Wearable transdermal electrical stimulation devices and methods of using them

ABSTRACT

Described herein are devices, systems, and methods for transdermal electrical stimulation. Devices described herein can include self-contained, lightweight, and wearable components. The devices include a primary unit including a first transdermal electrode and a secondary unit including a second transdermal electrode. The device can be capable of wireless communication. The primary unit and secondary unit are placed at two locations on the skin of a user, for example on the head or neck of a user. The first and second transdermal electrodes are electrically connected. Electrical stimulation is driven between the two electrodes. The electrical stimulation induces a cognitive effect in a user of the device.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of U.S. Provisional PatentApplication No. 61/729,851, filed Nov. 26, 2012, titled “DISPOSABLE ANDSEMI-DISPOSABLE TRANSCRANIAL ELECTRICAL STIMULATION SYSTEMS;” U.S.Provisional Patent Application No. 61/765,795, filed Feb. 17, 2013,titled “TRANSCRANIAL ELECTRICAL STIMULATION SYSTEMS;” U.S. ProvisionalPatent Application No. 61/767,945, filed Feb. 22, 2013, titled“TRANSCRANIAL NEUROMODULATION SYSTEMS;” U.S. Provisional PatentApplication No. 61/770,479, filed Feb. 28, 2013, titled “TRANSCRANIALNEUROMODULATION CONTROLLER AND DELIVERY SYSTEMS;” U.S. ProvisionalPatent Application No. 61/841,308, filed Jun. 29, 2013, titled“TRANSCRANIAL ELETRICAL STIMULATIONS SYSTEMS;” U.S. Provisional PatentApplication No. 61/845,845, filed Jul. 12, 2013, titled “TRANSCRANIALELECTRICAL STIMULATION SYSTEMS AND METHODS;” U.S. Provisional PatentApplication No. 61/875,424, filed Sep. 9, 2013, titled “TRANSCRANIALELECTRICAL STIMULATION SYSTEMS AND METHODS;” U.S. Provisional PatentApplication No. 61/900,880, filed Nov. 6, 2013, titled “NEUROMODULATIONCONTROL AND USER INTERFACE SYSTEMS;” U.S. Provisional Patent ApplicationNo. 61/875,891, filed on Sep. 10, 2013, titled “SYSTEMS AND METHODS FORTRANSCRANIAL ELECTRICAL STIMULATION DURING A PERFORMANCE OR GROUPINVENT;” U.S. Provisional Patent Application No. 61/888,910, filed onOct. 9, 2013, titled “TRANSCRANIAL ELECTRICAL STIMULATION SYSTEMS ANDMETHODS;” U.S. Provisional Patent Application No. 61/907,394, filed onNov. 22, 2013, titled “TRANSCRANIAL ELECTRICAL STIMULATION SYSTEMS ANDMETHODS,” each of which is herein incorporated by reference in itsentirety.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference in their entirety to the sameextent as if each individual publication or patent application wasspecifically and individually indicated to be incorporated by reference.

FIELD

The present application relates to apparatuses (e.g., systems anddevices) and methods for noninvasive neuromodulation to elicit acognitive effect using transdermal electrical stimulation.

BACKGROUND

The brain is composed of neurons and other cell types in connectednetworks that process sensory input, generate motor commands, andcontrol other behavioral and cognitive functions. Neurons communicateprimarily through electrochemical pulses that transmit signals betweenconnected cells within and between brain areas. Stimulation technologiesthat affect electric fields and electrochemical signaling in neurons canmodulate the pattern of neural activity and cause altered behavior,cognitive states, perception, and motor output.

Electrical stimulation applied to the head and neck area, such astranscranial electric stimulation (TES) through scalp electrodes, hasbeen used to affect brain function in the foiin of transcranialalternating current stimulation (tACS), transcranial direct currentstimulation (tDCS), and transcranial random noise stimulation (tRNS).Relative to tDCS, tACS and tRNS offer the advantage of reductions inpain, tingling, and other side effects on the scalp. Another strategy toreduce side effects is to use a high-density-tDCS (HD-tDCS) system withsmaller electrode pads, such as ones sold by Soterix Medical. tACS alsohas the advantage of being inherently temporal in nature and thuscapable of affecting, inducing, or destructively interfering withendogenous brain rhythms.

TES is advantageous for modulating brain activity and cognitive functionin man. TES has been shown to improve motor control and motor learning,improve memory consolidation during slow-wave sleep, regulatedecision-making and risk assessment, affect sensory perception, andcause movements. Systems and methods for TES have been disclosed (seefor example, U.S. Pat. No. 4,646,744 to Capel; U.S. Pat. No. 5,540,736to Haimovich et al.; U.S. Pat. No. 8,190,248 to Besio et al.; U.S. Pat.No. 8,239,030 to Hagedorn and Thompson; U.S. Patent ApplicationPublication No. 2011/0144716 to Bikson et al.; and U.S. PatentApplication Publication No. 2009/0177243 to Lebedev et al.). Many suchTES systems described in the prior art require surgical implantation ofcomponents for electrical stimulation on the head of a user (see forexample U.S. Pat. No. 8,121,695 to Gilner and U.S. Pat. No. 8,150,537 toTanaka and Nakanishi). Although tDCS systems with numerous electrodesand a high level of configurability have been disclosed (see, forexample, U.S. Patent Application Publication Nos. 2012/0209346,2012/0265261, and 2012/0245653 to Bikson et al.), as have portable TESsystems for auto-stimulation (U.S. Patent Application Publication No.2011/0288610 to Brocke), such prior art TES systems are complicated, andwould be difficult for an end-user (e.g., a patient or subject wearingthe device) to apply and operate.

The simplest form of TES is tDCS. Several open source tDCS projects havereleased designs for inexpensive TES systems, including the ‘ThinkingCap’ from Grindhouse Wetware and the Go Flow. In such examples, theelectronic circuitry requires a voltage supply (generally 9 V or 12 V);a current regulator to supply constant current as the impedance betweenan electrode and a subject's head changes slightly (e.g. due tomovement, sweating, etc.); and some circuitry to ensure that spikes ofcurrent do not pass into the subject. Additional components can be addedto select the current delivered, limit the time of stimulation, andprovide visual or other indicators of stimulation.

tACS requires additional hardware to deliver alternating currents to theelectrodes at an appropriate frequency. An oscillator, microcontroller,or timing circuit can be used to deliver a desired time-varyingstimulation. In some designs, a digital-to-analog converter is used.

tRNS additionally requires a microcontroller or other processorconfigured to provide random values with appropriate structure that arethen converted to an analog signal and used to gate current at a thedesired intensity (e.g. at a desired amplitude, frequency, and/orduration) through appropriate circuitry.

For each form of TES, one or more pairs of electrodes coupled to asubject's head or body are used to deliver the desired energy to thesubject's brain or nervous system. A battery or AC power supply is usedto supply power. For example, hardware and software systems for TEStypically include: a battery or power supply safely isolated from mainspower by magnetic, optic, or other techniques; control hardware and/orsoftware for triggering a TES event and controlling the waveform,duration, intensity, and other parameters of stimulation of eachelectrode; and one or more pairs of electrodes with gel, saline, oranother material for electrical coupling to the scalp. Such prior artapparatuses are typically cumbersome, and can be heavy and difficult tooperate and apply.

Historically, stimulation electrodes used in TES have been relativelylarge, on the order of about more than 2 cm by 2 cm. The motivation forlarge electrode pads has been to reduce the tingling, itchy, or painfulsensation created at the edge of the electrodes from the generatedelectric field. For instance, Feurra and colleagues used a 3 cm×4 cmelectrode and a 5 cm×7 cm electrode for stimulating somatosensory cortex(Feurra et al., 2011a). Bikson and coinventors have proposed a ‘highdensity’ electrode system with multiple smaller electrodes arranged ingroups and improved coupling of the electrical fields to the scalp inorder to reduce discomfort (U.S. patent application Ser. No. 12/937,950,titled “Apparatus and Method for Neurocranial Electrostimulation” byinventors Marom Bikson, Abhishek Datta, Fortunato Battaglia, MagedElwassif).

Similarly, Schutter (Schutter and Hortensius, 2011) usedconductive-rubber electrodes placed in wet sponges saturated with ParkerSpectra 360 electrode gel (Parker Laboratories, Fairfield, USA). Otherskin surface mounted electrodes known to be employed in TES includeadhesive stimulation electrodes that maintain positioning by adhering tothe scalp. In other embodiments, a band, helmet, or other head-mountedassembly maintains the positioning of the stimulation electrodes. Ingeneral, these prior art systems all include electrodes that may beattached to the subject and are connected, typically by a wire or otherconnector, to a base unit that is remotely located from the electrodesand the subject's head. These base units may include thestimulator/controller for applying the waveforms.

Various commercial and custom systems for triggering a specifiedstimulus waveform using one or more pairs of TES electrodes have beendescribed and are well known to one skilled in the art of brainrecording or TES, e.g. DS2 or DS3 Isolated Stimulator (Digitimer Ltd.,Welwyn Garden City, Hertfordshire, U.K.). Such systems are not typicallyportable or wearable, at least in part because of subject safetyconcerns; in order to provide sufficient power (current, voltage) to asubject to produce an effect, many systems require bulky and durablesignal conditioning and electrical isolation, and therefore physicallyisolate these control units from the subject (and particularly thesubject's head).

Described herein are apparatuses (devices, systems, etc.) that mayprovide effective stimulation (e.g., TES) to produce a cognitive effectin a subject, yet be intuitive and easy to apply and operate and may belightweight, durable and self-contained, so that the entire apparatus(electrodes and stimulator) can be applied and worn on the subject's(patient's) head. Some or all of the control functions for the apparatusmay be remotely controlled, e.g., using non-transient control logicexecutable on a remote processing device (e.g., smartphone, pad,computer, etc.). The apparatuses and methods of making and using them,described herein may address many of the shortcomings and maydramatically improve upon prior art TES apparatuses and methods.

Also described herein are exemplary brain stimulation techniques thatare known in the art can also be combined with (and improved upon by)TES to create advantageous forms of neuromodulation. For example,transcranial ultrasound neuromodulation employs ultrasound forstimulating neural tissue rather than for imaging, see, for example,U.S. Patent Application Publication No. 2011/0178441 and InternationalPatent Application No. PCT/US2010/055527 (Publication No. WO2011/057028). Such parallel or additional techniques may includetranscranial magnetic stimulation, optogenetic stimulation, andelectrocorticography.

Transcranial magnetic stimulation (TMS) induces electric fields in thebrain by generating a strong (generally pulsed) magnetic field with acoiled electromagnet at or near the head. The magnetic field istransmitted painlessly and efficiently through the skin and skull to theunderlying neural tissue. Deep brain stimulation (DBS) requiresimplantation of electrodes targeted to a brain area of interest,generally one at some depth from the brain surface. A long thinelectrode assembly, generally with several conductive leads near the tipdelivers electrical stimulation to a tissue of interest. DBS is aneffective strategy for treating Parkinson's disease in subjectsunresponsive to drugs.

Optogenetic stimulation uses light of a specified wavelength to activatean engineered protein expressed in neurons or other cell types thatmodifies the electrical and/or biochemical activity of a targeted cell.For deep brain applications, light is generally introduced via animplanted optical fiber.

Electrocorticography (ECoG) arrays are electrodes implanted on thesurface of the brain or dura. ECoG arrays can be used to recordelectrical potentials and/or stimulate underlying cortical tissue, forinstance to map the focal point of a seizure.

SUMMARY OF THE DISCLOSURE

In general, described herein are lightweight and wearable transdermalelectrical stimulation apparatuses for inducing a cognitive effect in asubject. In particular, described herein are lightweight and wearabletransdermal electrical stimulation apparatuses that are self-contained.The apparatus may include all of the elements necessary and sufficientto drive stimulation and achieve a predetermined cognitive effect. Theapparatus may be untethered from any component that is not worn orwearable with the rest of the apparatus; for example, the entireapparatus may be attached and worn on the head and/or neck of thesubject. Although the apparatus may be self-contained, it may beconfigured to receive instructions from one or more remote systems (andmay transmit signals to the same or a different remote system),including instructions that select or modify stimulation parameters.

Also described herein are lightweight and wearable transdermalelectrical stimulation apparatuses for inducing a cognitive effect in asubject that include a durable portion that couples with a disposable orreplaceable portion to form the lightweight and wearable transdermalelectrical stimulation apparatus. The durable or reusable portion mayinclude a processor and/or controller, power source, and a connector forconnecting to two or more electrodes in the disposable portion to drivestimulation between the electrodes to induce a cognitive effect in asubject wearing the apparatus. As used herein, a disposable element mayrefer to a limited-use item (e.g., single-use or limited multiple-use,including 2-3 uses, 2-5 uses, 2-7 uses, 2-10 uses, or less than 5 uses,less than 10 uses, etc.). A disposable element may be used once (or 2-3times, etc.) and then removed from the apparatus and replaced with a newelement. In particular, the electrodes described herein may bedisposable elements that include a conductive material (e.g., conductivegel, conductive adhesive, etc.) and/or adhesive that is only reliablyuseful a limited number of times before needing to be replaced orrefurbished.

The apparatuses described herein include devices and systems which mayinclude multiple connected or connectable elements. These apparatusesmay be used or worn by a subject. The subject wearing or using thedevice may be referred to as a subject or operator. The apparatusesdescribed herein may be configured to provide one or more cognitiveeffects. In general, a cognitive effect may include any inducedcognitive effect that is perceived subjectively by the recipient as asensory perception, movement, concept, instruction, other symboliccommunication, or modifies the recipient's cognitive, emotional,physiological, attentional, or other cognitive state. For example, aneffect of electrical stimulation is one or more of inhibition,excitation, or modulation of neuronal activity. Specific examples ofcognitive effects may include relaxation, enhanced attention, moodelevation, increased energy (e.g., physiological arousal, increasedsubjective feelings of energy), or the like. Cognitive effects may bestereotypical across a population (though with individual variation anddegree) and may be demonstrated by any appropriate means, including bysubject reporting, objective testing, imaging, physiological recording,etc. Particular cognitive effects evoked may depend upon the position ofthe electrodes of the apparatus with respect to the subject, and/or thestimulation parameters described herein. The apparatuses describedherein may be optimized to achieve a specific cognitive effect.

A cognitive effect of neuromodulation may cause a change in a user'slevel of energy, fatigue, sleepiness, alertness, wakefulness, anxiety,stress, sensory experience, motor performance, formation of ideas andthoughts, sexual arousal, creativity, relaxation, empathy, and/orconnectedness that is detectable by an objective measurement (e.g.behavioral assay) and/or subjective report by the user.

For example, a cognitive effect of neuromodulation may cause a change inan emotional state of the user where the change is detectable by anobjective measurement (e.g. behavioral assay) and/or subjective reportby the user and an emotion affected is selected from the list includingbut not limited to: affection, anger, angst, anguish, annoyance,anxiety, apathy, arousal, awe, boredom, confidence, contempt,contentment, courage, curiosity, depression, desire, despair,disappointment, disgust, distrust, dread, ecstasy, embarrassment, envy,euphoria, excitement, fear, frustration, gratitude, grief, guilt,happiness, hatred, hope, horror, hostility, hurt, hysteria,indifference, interest, jealousy, joy, loathing, loneliness, love, lust,outrage, panic, passion, pity, pleasure, pride, rage, regret, relief,remorse, sadness, satisfaction, self-confidence, shame, shock, shyness,sorrow, suffering, surprise, terror, trust, wonder, worry, zeal, andzest.

In some variations, the cognitive effects evoked by the apparatusesdescribed herein may be positive cognitive effects; positive cognitiveeffects refers to cognitive effects resulting in an increase inalertness, an increase in relaxation, a decrease in fatigue, and adecrease in anxiety, an enhancement in motor performance, an increase inrecall, and an increase in empathy.

A cognitive effect of neuromodulation may cause a change in brainactivity measured by one or a plurality of: electroencephalography(EEG), magnetoencephalography (MEG), functional magnetic resonanceimaging (fMRI), functional near-infrared spectroscopy (fNIRS), positronemission tomography (PET), single-photon emission computed tomography(SPECT), computed tomography (CT), functional tissue pulsatility imaging(fTPI), xenon 133 imaging, or other techniques for measuring brainactivity known to one skilled in the art.

A cognitive effect of neuromodulation may be detectable by aphysiological measurement of a subject, including but not limited tomeasurements of the following: brain activity, body temperature,electromyogram (EMG), galvanic skin response (GSR), heart rate, bloodpressure, respiration rate, pulse oximetry, pupil dilation, eyemovement, and gaze direction.

A cognitive effect of neuromodulation may be detectable by a cognitiveassessment that takes the form of one or more of: a test of motorcontrol, a test of cognitive state, a test of cognitive ability, asensory processing task, an event related potential assessment, areaction time task, a motor coordination task, a language assessment, atest of attention, a test of emotional state, a behavioral assessment,an assessment of emotional state, an assessment of obsessive compulsivebehavior, a test of social behavior, an assessment of risk-takingbehavior, an assessment of addictive behavior, a standardized cognitivetask, an assessment of “cognitive flexibility” such as the Stroop task,a working memory task (such as the n-back task), tests that measurelearning rate, or a customized cognitive task.

In particular, the lightweight and wearable apparatuses described hereinmay include a pair of electrodes arranged so that one electrode iscoupled closely and/or directly to a controller/processor controllingstimulation and a second electrode that is tethered to the firstelectrode and/or the controller/processor by a cable (e.g., cord, wire,ribbon, etc.) to permit independent positioning of the first and secondelectrodes on the subject's head and/or neck. The cable connectionbetween the first and second electrodes is typically configured to passcurrent to the electrode for stimulation and may be of an appropriatelength (e.g., less than about 18 inches, less than about 17 inches, lessthan about 16 inches, less than about 15 inches, less than about 14inches, less than about 13 inches, less than about 12 inches, less thanabout 11 inches, less than about 10 inches, less than about 9 inches,less than about 8 inches, less than about 7 inches, less than about 6inches, between about 3-4 inches, between about 3-6 inches, betweenabout 3-10 inches, between about 3-12 inches, etc.). The electrodes maybe skin-contact electrodes and may be configured to include an adhesivewhich may be an electrically conductive adhesive to hold the electrodesand/or apparatus to the subject's head/neck.

For example, a lightweight and wearable transdermal electricalstimulation device for inducing a cognitive effect in a subject mayinclude a primary unit and a secondary unit. The primary unit mayinclude a power source, a controller, and a first transdermal electrode.The secondary unit may be electrically connected to the primary unit bya cable extending from the primary unit and may include a secondtransdermal electrode. One or both of the primary unit and the secondaryunit may be configured to be worn on the subject's head or neck and thesecondary unit may be configured to be independently positioned on thesubject relative to the primary unit, so that the controller can drivestimulation between the first and second electrodes to induce acognitive effect in the subject.

In general, the primary unit may include (or may be) a durable componentthat may be re-used with different disposable components. The primaryunit may include a controller to control stimulation across theelectrodes of the apparatus, a lightweight power source (e.g., battery,capacitive power source, etc.), and an electrode or connector to anelectrode. The controller may be configured to apply one or morepre-determined stimulation protocols when driving stimulation betweenthe first and second electrodes to induce a cognitive effect. Thesecondary unit may correspond to a disposable portion, and may includeone more (e.g., 2, 3, 4, or all) electrodes and/or the connector (cable,cord, wire, ribbon, etc.) between the second electrode and the primaryunit. The primary and secondary units may be referred to as master andslave components/units. The primary and second units may be configuredto couple together before being applied to the subject. For example, thesecondary unit may be configured to be detachably coupled to the primaryunit before applying the primary and secondary units to the subject.

In general, the primary unit may be configured to be adhesively attachedto the subject's head or neck.

As mentioned, any of the variations described herein may be adapted tobe lightweight and wearable. For example, the combined weight of aprimary unit and secondary unit together may be less than about 8 ounces(e.g., less than about 6 ounces, less than about 5 ounces, less thanabout 4 ounces, less than about 3 ounces, less than about 2 ounces, lessthan about 1.5 ounces, less than about 1 ounce, less than about 0.5ounces, less than about 0.25 ounces, etc.). Generally, an apparatushaving an overall weight of less than about 3 ounces is particularhelpful. Further, the device may be adapted for wearability by limitingthe dimensions (height) of the device above the surface of the subject'sskin. For example, the apparatus may have a maximum thickness of theprimary unit (and/or the secondary unit) that is less than about 30 mm(e.g., less than about 25 mm, less than about 20 mm, less than about 15mm, less than about 10 mm, less than 5 mm, etc.). The thickness (whichmay also refer to as height) of the device may refer to the maximumamount that the applicator extends from the skin when worn.

The apparatuses described herein may be configured as TES apparatus(transcranial electrical stimulator; however, it should be understoodthat in some variation the cognitive effect may arise from one or acombination of stimulation effects, including stimulation of nerves(e.g., cranial nerves) and/or brain cells. Any appropriate electricalstimulation may be applied by the apparatus to provoke the desiredcognitive effect. For example, a controller may be configured to causealternating current, direct current, or a combination of alternating anddirect current between the first and second electrodes.

In general, the apparatus may be formed into an assembly in which thesecondary unit, which includes the second electrode, is tethered by acable making electrical communication with the primary unit and theprimary and secondary units are engaged with each other to form theapparatus; before being applied to the subject, the secondary unit maybe separated from the primary unit while remaining coupled via the cableto the primary unit, and independently applied to the head, neck, orshoulder of the subject. Both the primary and secondary unit may bepositioned on the subject's head and/or neck.

The apparatus may include one or more indicators on the primary and/orsecondary units to indicate function or control of the apparatus. Forexample, the apparatus may include a visual indicator on an outersurface of the primary unit. The apparatus may include an input controlon an outer surface of the primary unit.

As mentioned, the first and second electrode may be configured to bedisposable and replaceably detachably attached to the device. Thus, insome variations the primary unit includes a connector to a disposable(primary) electrode and is also configured to connect to the secondaryelectrode, e.g., through the cable. For example, the first electrode maybe part of a replaceable cartridge configured to be releasablydetachably coupled to the primary unit. The first electrode and thesecondary unit may be part of a replaceable cartridge configured to bereleasably detachably coupled to the primary unit.

Any of the variations described herein may be configured so that thecontroller regulates the applied energy (e.g., current) by adjusting theapplied current based on a detected resistance/impedance between theelectrodes. For example, the controller may be configured to adjustcurrent across the first and second electrodes based on a detectedimpedance.

The primary unit further may comprise a wireless communications modulein communication with the controller and configured to providestimulation instructions to the controller. Thus, although the apparatusmay operate independently (e.g., without a connection either remote orlocal) to a separate processor providing control/feedback, in somevariations the apparatus may include a connection to a remote processorthat provides control and/or feedback on operation of the device. Forexample, the remote processor may select and/or instruct the apparatuswhat parameters to apply to provide a particular cognitive effect,and/or to coordinate the application of the stimulation parameters.

As mentioned, the apparatus may be configured to apply any appropriatestimulation protocol to provoke the desired cognitive effect. Forexample, a device may be configured to apply pulsed electricalstimulation.

In general, the apparatuses described herein may be configured to bepositioned on the head and/or neck of the subject in positions adaptedto invoke a particular cognitive effect when stimulation is applied. Forexample, the second electrode may be configured to be positioned on aneck or head of a subject.

Also described herein are methods of operating such devices, includingmethods of inducing a cognitive effect in a subject. For example, amethod of inducing a cognitive effect may include attaching a primaryunit of a lightweight, wearable, and self-contained transdeimalelectrical stimulation device to a first location so that a firstelectrode of the primary unit contacts the subject's skin. The methodmay further comprise attaching a secondary unit comprising a secondelectrode to a second location on the subject, wherein the secondaryunit is electrically connected to the primary unit by a cable. One orboth of the first location and second location is on the subject's heador neck. The method may also include driving stimulation between thefirst and second electrodes to induce a cognitive effect in the subject,wherein a controller in the primary unit drives stimulation.

In any of the variations described herein, the method may also includeseparating the primary unit from the secondary unit before drivingstimulation between the first and second electrodes. This separation maybe performed after connecting any disposable elements to the reusableelements. Separation may involve removing the secondary unit from theprimary unit so that the cable extends between the two; the cable may becontained within (e.g., between) the primary and secondary unit, and mayextended to allow independent positioning of the primary and secondaryunits on the subject. For example, the secondary unit may be separatedfrom the primary unit by unwinding the cable to increase the distancebetween the two units.

Either or both the primary and secondary units may be adhesivelyattached directly to the subject. For example, attaching the primaryunit may comprise adhesively attaching the primary unit to the subject'shead or neck at the first location. Attaching the secondary unit maycomprise adhesively attaching the secondary unit to the subject.Attaching the secondary unit may comprise attaching the secondary unitto the subject's neck or head. The primary and secondary units mayinclude a biocompatible adhesive; the adhesive may extend over theelectrodes in the primary and secondary unit, or it may be separatedfrom the electrodes. Adhesive over the electrodes may be a conductiveadhesive.

In some variations, the methods may include selecting which stimulationparameter(s) to operate the apparatus when driving stimulation. Theapparatus may include one or more controls on the device to allowselection of the driving stimulation (e.g., selection based on thedesired cognitive effect(s), power levels, power on/off, etc.). In somevariations the method includes manually selecting the stimulationparameters (e.g., by the user directly). In some variations, the methodof operation may also or alternatively include wirelessly transmittingstimulation parameters (e.g., from a mobile communications device, etc.)to the controller in the primary unit.

Any appropriate stimulation parameters may be used, but effectivestimulation parameters may include driving stimulation between the firstand second electrodes to induce the cognitive effect in the subject maycomprises supplying a maximum current of at least 2 mA duringstimulation. Driving stimulation between the first and second electrodesto induce the cognitive effect in the subject may comprise supplyingcurrent at a frequency of about 400 Hz-20 kHz (e.g., between about 500Hz-10 kHz, or specifically, between 650 Hz-10 kHz, or greater than 640Hz).

In some variations of the methods of operating the devices describedherein, the methods may include attaching a cartridge including thefirst electrode to the primary unit before attaching the primary unit tothe subject's head or neck.

As mentioned above, any of the lightweight and wearable apparatusesdescribed herein may be self-contained and configured to wirelesslyreceive controlling instructions from a remote site. For example, alightweight and wearable transdermal electrical stimulation device forinducing a cognitive effect in a subject may include a primary unit anda secondary unit. The primary unit may include a power source, awireless communications module, a controller configured to receiveinstructions from a remotely located processor via the wirelesscommunications module, and a first transdermal electrode. The secondaryunit may include a second transdermal electrode and is electricallyconnected to the primary unit by a cable extending from the primaryunit. Either or both the primary unit and the secondary unit may beconfigured to be worn on the subject's head or neck, and the secondaryunit is configured to be independently positioned at a second locationon the subject relative to the primary unit so that the controller candrive stimulation between the first and second electrodes to induce acognitive effect in the subject.

The secondary unit may be configured to be detachably coupled to theprimary unit before driving stimulation between the first and secondelectrodes, and may be configured to be separated from the primary unitbefore being applied.

As mentioned above, any of the apparatuses described herein may be wornon the head and/or neck. For example, the primary unit may be adhesivelyattached to the subject's head or neck. In some variations the primaryunit is secured to the subject by a strap (e.g., headband, etc.) orother item (e.g. wearable support structure) instead of or in additionto an adhesive attachment. For example, the primary unit may be clippedonto a set of glasses or worn over the subject's ear(s), etc.

As also mentioned above, any of the apparatuses described herein mayinclude an indicator, such as a visual indicator on the apparatus (e.g.,on the primary and/or secondary units). For example, the apparatus mayinclude a visual indicator on an outer surface of the primary unit, suchas an LED. The visual indicator may indicate communication status (e.g.,receiving instructions, sending data, etc.), power status (on/off),stimulation protocol (e.g., target cognitive state, etc.), or the like.

Any of the apparatuses described herein may also include one or moremanual inputs and/or controls. For example, a device may include aninput control on an outer surface of the primary unit and/or secondaryunit. The input may be a button, dial, switch, etc. For example, aninput may be a button for controlling the power on/off state.

Any of the apparatuses described herein may include one or more inputsand/or controls to allow selection of the stimulation parameters. Ingeneral the stimulation parameters may be selected based on apredetermined menu of parameter values (e.g., selecting the stimulationprotocol based on the desired cognitive effect, and/or pre-customizedstimulation parameters for a particular user or class of users, etc.).For example, the apparatus may receive controlling stimulationinstructions that control one or more of: current amplitude, currentfrequency, pulse width, pulse duration, pulse frequency, pulse wavefoim,burst duration, burst frequency, off-time, burst waveform, positive dutycycle, negative duty cycle, and on/off.

Also described herein are non-transitory computer-readable storagemediums storing a set of instructions capable of being executed by aremote processor (and particularly a smartphone or the like), that whenexecuted by the smartphone causes the smartphone to allow a subject toselect one or more (or a set) of control parameters for controlling thelightweight, wearable apparatuses described herein. The set ofinstructions may include confirming a communication link with one ormore lightweight, wearable apparatuses, presenting a list and/or menu ofpre-selected control values (e.g., for one or more of current amplitude,current frequency, pulse width, pulse duration, pulse frequency, pulsewaveform, burst duration, burst frequency, off-time, burst waveform,positive duty cycle, negative duty cycle, and on/off, etc.), or forallowing modification of one or more of these control values separately.The set of instructions may also permit transmission of the controlvalues to the apparatus or an index to select from a list of possiblepredetermined profiles of such control values in the apparatus. The setof instructions may also allow the subject to turn the device on/off.

The set of instructions may also include instructions and/or guidancefor applying the device (e.g., both primary and secondary units) to theproper positions on the body. For example the set of instructionsexecutable on the remote processor may include displaying one or morediagrams indicating where on the subject to position the first andsecond electrodes of the primary and secondary device components.

The lightweight, wearable apparatus may be configured for wirelesslycommunication with the remote processor by any appropriate wirelesstechnique, including (but not limited to) electromagnetic (e.g., RF,UWB, etc.), ultrasound, or the like. For example, the wirelesscommunications module of the lightweight, wearable apparatus maycomprise a Bluetooth transmitter.

A lightweight, wearable and self-contained transdermal electricalstimulation device for inducing a cognitive effect in a subject may alsoor alternatively include a primary unit having a housing and a secondaryunit electrically connected to the primary unit by a cable extendingfrom the housing. The housing of the primary unit may at least partiallyenclose a power source; a wireless communications module; a currentgenerator connected to the power source; a controller configured toreceive stimulation instructions from a remotely located processor viathe wireless communications module; and a replaceable cartridgeincluding a first transdermal electrode. The secondary unit may includea second transdeiinal electrode. Either or both the primary unit and thesecondary unit may be configured to be worn on the subject's head orneck and the secondary unit may be configured to be independentlyattached to a second location on the subject independently of theprimary unit (though tethered to the primary unit) so that thecontroller controls the current generator to drive stimulation betweenthe first and second electrodes based on stimulation instructionsreceived from the remotely located processor to induce a cognitiveeffect in the subject.

A method of inducing a cognitive effect in a subject may includewireless communication control instructions to the apparatus from aremote processor. For example, a method of inducing a cognitive effectmay include attaching a primary unit of a lightweight and wearabletransdermal electrical stimulation device to a first location on thesubject so that a first electrode of the primary unit contacts thesubject's skin. The method may further comprise attaching a secondaryunit comprising a second electrode to a second location on the subject,wherein the secondary unit is electrically connected to the primary unitby a cable. Either or both the first location and the second locationmay be on the subject's head or neck. The method may include wirelesslyreceiving stimulation information in the primary unit and drivingstimulation between the first and second electrodes to induce acognitive effect in the subject.

As mentioned, wirelessly receiving may include wirelessly receivingstimulation parameters from a remote processor, wherein the stimulationparameters include at least one of current amplitude, current frequency,pulse width, pulse duration, pulse frequency, pulse waveform, burstduration, burst frequency, off-time, and burst waveform, positive dutycycle, negative duty cycle, and on/off. In some variations the remoteprocessor transmits an index value that corresponds to a choice from amenu of preset stimulation parameters in the apparatus. Transmittedcontrol instructions may include both an index value and one or moremodification of the stimulation parameters such as current amplitude,current frequency, pulse width, pulse duration, pulse frequency, pulsewaveform, burst duration, burst frequency, off-time, and burst waveform,positive duty cycle, negative duty cycle, and on/off.

A method of inducing a cognitive effect in a subject may compriseadhesively securing a primary unit of a lightweight and wearabletransdermal electrical stimulation device to a first location on thesubject's head or neck so that a first electrode of the primary unitcontacts the subject's skin. The method may also include attaching asecondary unit comprising a second electrode to a second location on thesubject's head or neck, wherein the secondary unit is electricallyconnected to the primary unit by a cable. Stimulation controlinformation may be wirelessly transmitted to the primary unit from aremote processor. The method may include applying the stimulationcontrol information to drive stimulation between the first and secondelectrodes to induce a cognitive effect in the subject.

As mentioned, any of the apparatuses described herein may be configuredso that they include a durable (reusable) portion and a disposable(e.g., limited-use, single-use, non-durable, etc.) component. Ingeneral, the electrodes and/or cable connecting the second electrode tothe primary unit may be disposable, while the processor/controller isdurable. The non-durable or disposable components may be formed as acartridge that couples to the durable components. The disposablecomponents may also be referred to as removable and/or replaceablecomponents, as they may be swapped out between uses.

For example a lightweight and wearable transdermal electricalstimulation apparatus for inducing a cognitive effect in a subject isprovided. The apparatus comprises a primary unit configured to be wornon the subject (including on the subject's head and/or neck) andincluding a power source, a controller and an electrode connector. Theapparatus further comprises a disposable first electrode configured todetachably connect to the primary unit via the electrode connector. Theapparatus comprises a disposable second electrode configured todetachably electrically connect to the controller via a cable extendingfrom either the primary unit or the first electrode. Either the primaryor secondary units or both the primary and secondary units arepositioned on the subject's head and/or neck. The second electrode isconfigured to be independently positioned at a second location on thesubject relative to the first electrode of the primary unit (althoughflexibly tethered to the primary unit by the cable) so that thecontroller can drive stimulation between the first electrode and thesecond electrode to induce a cognitive effect in the subject.

In another aspect, a method of inducing a cognitive effect in a subjectis provided. The method comprises coupling a disposable first electrodeand disposable second electrode to a reusable primary unit of alightweight and wearable transdermal electrical stimulation apparatus,wherein the disposable first electrode is coupled to the primary unitvia an electrode connector on the primary unit so that the firstelectrode is attached to the primary unit and in electricalcommunication with a controller in the primary unit, and wherein thesecond electrode is electrically connected to the controller via acable. The method further comprises attaching the primary unit to afirst location (e.g., on the subject's head or neck) so that the firstelectrode contacts the subject's skin. The method comprisesindependently attaching the second electrode to a second location on thesubject (e.g., on the subject's head or neck) so that the secondelectrode contacts the subject's skin. The method comprises activatingthe controller to drive stimulation between the first and secondelectrodes to induce a cognitive effect in the subject.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B show front perspective and side perspective views,respectively, of one variation of a lightweight, wearable andself-contained electrical stimulation apparatus, as described herein.

FIGS. 1C and 1D show side perspective and top views of the apparatus ofFIGS. 1A and 1B. FIG. 1E shows a side view of the apparatus of FIGS.1A-1D.

FIG. 2A shows a side perspective view of the apparatus of FIGS. 1A-1Bwith a cover removed, showing the secondary unit (includingskin-contacting electrode) positioned above the primary unit (includingskin-contacting electrode).

FIG. 2B shows an alternative view of the apparatus of FIG. 2A. FIG. 2Cillustrates the apparatus of FIG. 2B with the secondary unit separatedfrom the primary unit.

FIG. 3A is a side view of a primary electrode portion of a primary unitfor an apparatus such as the one shown in FIG. 2A.

FIG. 3B is a top perspective view of a primary unit including theprimary electrode portion of FIG. 3A.

FIG. 3C is another view of the primary unit shown in FIG. 3B with theouter side housing removed.

FIG. 4A shows on example of a secondary unit of an apparatus such as theapparatus of FIGS. 1A-3C.

FIG. 4B shows a partially transparent view of the secondary unit of FIG.4A. FIG. 4C is a bottom view of the secondary unit of FIG. 4A.

FIG. 5A illustrates some of the components that may be arranged and heldwithin the housing of the primary unit.

FIG. 5B is a side perspective view of FIG. 5A.

FIG. 6 illustrates an embodiment of an AC stimulation protocol.

FIG. 7 illustrates an embodiment of a DC stimulation protocol.

FIGS. 8A-8C illustrate embodiments of example waveforms and electrodeconfigurations.

FIG. 9A shows standard model anatomy in which two large electrodes havebeen placed over the motor cortex (anode) and orbitofrontal cortex(cathode), and FIG. 9B shows the resulting electric potentials on thescalp; FIG. 9C shows the absolute magnitude of the electric field on thescalp. Similarly, FIG. 9D. shows the absolute magnitude of the electricfield in the brain from the arrangement shown in FIG. 9A. FIG. 9E showsthe direction and magnitude of electric fields in the brain.

FIGS. 10A-10D show the results of FEM analysis with electrodes arrangedin a triangle shaped configuration over premotor cortex. The anode isplaced in the center and the cathodes are placed in the trianglecorners, as shown in FIG. 10A. FIG. 10B shows the distribution ofelectric potential on the scalp from this arrangement, FIG. 10C showsthe distribution of electric potential in the brain, and FIG. 10D showsthe absolute magnitude of the electric field in the brain.

FIGS. 11A-D show the results of FEM analysis with concentric ringelectrodes. The anode is placed over the premotor cortex, and thecathode surrounds the anode. FIG. 11B shows the electric potential onthe scalp, and FIG. 11C shows the resulting distribution of electricpotential in the brain. FIG. 11D shows the resulting absolute magnitudeof the electric field in the brain.

FIGS. 12A-D show the results of FEM analysis with a large central anodeplaced over premotor cortex and a thin outer electrode, as shown in FIG.12A. FIG. 12B shows the resulting electric potential on the scalp, andFIG. 12C shows the resulting electric potential in the brain. FIG. 12Dshows the resulting absolute magnitude of electric fields in the brain.

FIG. 13 illustrates another embodiment of an electrical stimulationdevice.

FIGS. 14A and 14B illustrate embodiments of an electrical stimulationdevice.

FIGS. 15A-15D illustrate another embodiment of an electrical stimulationdevice.

FIGS. 16A and 16B illustrate one variation of an apparatus including adisposable portion and a durable (reusable) portion. FIG. 16Billustrates the disposable portion positioned within a blister pack.

FIG. 17 illustrates a flexible support disk for a secondary unit,supporting one or more electrodes and having one or more relief cuts toincrease flexibility of the device.

FIG. 18A shows a disposable portion of one variation of an apparatusthat is configured to snap into a durable portion of the apparatus.

FIG. 18B shows the disposable portion snapped into position within themain housing of the primary unit.

FIG. 19A shows an optional backer on one side of a disposable portion ofthe apparatus (covering one or more electrodes and an adhesive).

FIG. 19B shows the disposable portion including the electrodes.

FIG. 20A illustrates the separation of a disposable component includingthe electrodes and adhesive from a durable holding component when thetwo are attached, as shown in FIG. 18B.

FIG. 20B shows the adhesive, electrodes and backer assuming a curvedconfiguration, e.g., on the curvature of the body part onto which it isplaced.

FIG. 21 shows the disengagement of a disposable portion from a durablemain housing by pushing on the center of the disposable portion,indicated with an arrow, to release the housing from the disposableportion.

FIG. 22 shows the disengagement of the disposable portion from the skinof a subject by peeling from the skin.

FIGS. 23A and 23B illustrate the location of an integrated replaceableor disposable battery on the underside of a housing. In FIG. 23A thebattery door is open, while in FIG. 23B the battery door is closed.

FIGS. 24A-24F shows a variation of a lightweight and wearable apparatusfor transdermal stimulation (e.g., TES) having a four electrodeconfiguration that is configurable with additional or fewer electrodesin various positions. FIG. 24A shows the electrodes at equidistantpositions on a track. FIG. 24B shows the electrodes and holder (primaryunit) of FIG. 24A with the electrodes arranged asymmetrically. FIG. 24Cshows another arrangement of the electrodes and holder (primary unit) ofFIG. 24A. FIG. 24D shows another arrangement of the electrodes andholder (primary unit) of FIG. 24A. FIG. 24E shows another arrangement ofthe electrodes and holder (primary unit) of FIG. 24A with the electrodesarranged asymmetrically. FIG. 24F shows another arrangement of theelectrodes and holder (primary unit) of FIG. 24A.

FIGS. 25A-25C illustrate configurable electrode configurations that maybe used with the apparatuses described herein. In FIG. 25A electrodesare arranged concentrically and various concentric rings may beconnected together to form the cathode or the anode. FIG. 25B shows asimilar configurable system for focusing electric fields using atriangle configuration. FIG. 25C shows another variation having a pieconfiguration of electrodes.

FIG. 26 is a schematic illustration of a lightweight, wearable andself-contained electrical stimulation apparatus.

FIGS. 27A-27D schematically illustrates non-transitory control logicthat causes a remote processor (e.g., of the computer, smartphone, etc.)to wirelessly transmit control instructions to a lightweight, wearable,and self-contained electrical stimulation apparatus. FIG. 27A shows aworkflow for configuring, actuating, and ending a TES session. FIG. 27Bshows components of a portable, wired TES system (e.g., lightweight,wearable, and self-contained apparatus for TES to induce a cognitiveeffect). FIG. 27C shows components of a TES system that connectswirelessly to a remote control unit having a microprocessor. FIG. 27D isa schematic of control logic that causes a remote processor (e.g., ofthe computer, smartphone, etc.) to wirelessly transmit controlinstructions to a lightweight, wearable, and self-contained electricalstimulation apparatus

FIG. 28A shows another variation of a lightweight, wearable andself-contained electrical stimulation apparatus including a primary unithaving a secondary unit tethered by a cable.

FIG. 28B illustrates the apparatus of FIG. 28A worn on a subject.

DETAILED DESCRIPTION

Lightweight and wearable apparatuses for applying transdermal electricalstimulation and methods of using them for inducing a cognitive effectare described. These apparatuses are typically self-contained,lightweight, and wearable devices and/or systems that include a primaryunit and at least one secondary unit. The primary unit can include afirst transdermal electrode, a processor or controller, which mayinclude current controller, for applying current and, in someembodiments, a wireless communications module. The system also typicallyincludes a secondary unit that is electrically connected to the primaryunit by a cable such as a wire, cord, ribbon, etc. The secondary unitalso typically includes a second transdermal electrode. The primary andsecondary unit may be initially and conveniently stored together in asingle housing (e.g., cover) and may be separated before applying orwhen applying to the subject's head and/or neck. The entireself-contained apparatus may be applied to and worn on the subject'shead and/or neck, and the secondary unit is generally tethered to theprimary unit by the cable so that the primary and secondary units can beindependently connected to the subject and are connected only to eachother by the cable, without requiring any additional cable connections.The apparatus can be configured to drive stimulation between the firstand second electrode to induce a cognitive effect in the subject (forexample, relaxation or excitement) while reducing any discomfortexperienced by the subject at the locations where the electrodes arecontacting the skin.

All of the components of the electrical stimulation device may beself-contained in one or more housings, and the entire device can easilybe worn by a user. As described above, different components of thedevice can be worn by being adhered to skin of a user. Some or all ofthe components of the device can also or alternatively be held againstthe skin by an accessory such as a headband or wrap; alternatively oradditionally the apparatus may be worn connected to an eyepiece orearpiece (e.g., eyeglasses, etc.). The simple wearability of the devicecan advantageously make it more comfortable and convenient to use for auser. It can also enhance the aesthetic effect of the device while beingworn and/or used by a subject. The device may be particularly andspecifically adapted to be wearable and lightweight; for example, theapparatus may weigh less than a predetermined amount (e.g., less than 8ounces, less than 7 ounces, less than 6 ounces, less than 5 ounces, lessthan 4 ounces, less than 3 ounces, less than 2 ounces, less than about1.5 ounces, less than about 1 ounce, less than about 0.5 ounces, lessthan about 0.25 ounces). The primary unit and the secondary unit mayalso be relatively flat or thin when worn against the head and/or neck(e.g., may be less than 30 mm thick, less than 25 mm thick, less than 20mm thick, less than about 10 mm, less than 5 mm, etc.).

The lightweight and wearable transdermal electrical stimulationapparatus for inducing a cognitive effect in a subject may generallyinclude hardware, software and/or firmware components that areconfigured to generate appropriate control sequences for the device,transmit signals to a current or voltage source and/or conditioner, andconnect to electrodes that are configured to be placed on a user forgenerating electrical currents. For example, the apparatus may comprisea controller configured to transmit sequences to a current generator.Thus, the apparatus may be configured for mobile use.

The apparatus may generally be configured to receive control informationfor controlling the stimulation. This control may include control of thestart, duration and timing of stimulation (e.g., on/off, duration, etc.)and/or may also include controls for the waveform to be applied toinduce a cognitive effect in a subject. In general, the inducedcognitive effect is a function of the position of the electrodes (e.g.,where on the head/neck the electrodes are positioned) and thestimulation parameters of the applied waveforms. An apparatus mayinclude one or more manual controls (e.g., inputs) on the apparatus,and/or it may include wireless communication to a remote processor(“base station”) that wirelessly transmits control information to theapparatus. For example, the apparatus may include a wireless module forwireless communication to the base station or via cellular networks tothe Internet. A remote processor may be configured to transmit controlsignals to a current generator located in the device (e.g., within theprimary unit). The remote processor may include non-transitorycomputer-readable storage mediums storing a set of instructions capableof being executed by a remote processor (such as a smartphone or thelike), that when executed by the remote processor causes the processorto allow a subject to select one or more (or a set) of controlparameters for controlling the lightweight, wearable apparatusesdescribed herein. The set of instructions may include confirming acommunication link with one or more lightweight, wearable apparatuses,presenting a list and/or menu of pre-selected control values (e.g., forone or more of current amplitude, current frequency, pulse width, pulseduration, pulse frequency, pulse waveform, burst duration, burstfrequency, off-time, burst waveform, positive duty cycle, negative dutycycle, and on/off, etc.), or for allowing modification of one or more ofthese control values separately.

In general, inducing a cognitive effect can include inducing a responsethat a reasonable user is cognitively aware of. The effect can include aphysiological change. For example, the effect can include a change inthe amplitude or phase of brain rhythms. The effect can include amodulation of one or a plurality of the following biophysical orbiochemical processes: (i) ion channel activity, (ii) ion transporteractivity, (iii) secretion of signaling molecules, (iv) proliferation ofthe cells, (v) differentiation of the cells, (vi) protein transcriptionof cells, (vii) protein translation of cells, (viii) proteinphosphorylation of the cells, or (ix) protein structures in the cells.The apparatus (device or system) may be configured so that the inducedcognitive effect is perceived subjectively by the recipient as a sensoryperception, movement, concept, instruction, other symboliccommunication, or modifies the recipient's cognitive, emotional,physiological, attentional, or other cognitive state. Neurons and othercells in the brain and head area are electrically active, so stimulationusing electric fields can be an effective strategy for modulating brainfunction. In various embodiments of the invention, the effect ofelectrical stimulation is one or more of inhibition, excitation, ormodulation of neuronal activity.

FIGS. 1A and 1B show perspective views of one variation of a wearableand lightweight apparatus 100 for applying transdermal electricalstimulation. The device shown in FIGS. 1A-1E includes a cover 102,although this cover may be optional. The cover 102 may allow storage ofboth the primary and secondary portions of the units together; prior tobeing applied, the cover may be removed and the secondary unit (andelectrode) separated from the primary unit, though connected by atethering cable (not visible in FIGS. 1A-1E). The primary unit 104portion of the apparatus show in FIGS. 1A-1E is partially visible. InFIGS. 1A, 1B and 1E, the apparatus is shown partially transparent; inFIGS. 1C and 1D, the outer cover 102 obscures the inner components.

FIGS. 1A-1E show the apparatus (device 100) including an input control106, for example a switch, touch-screen, button, or other user interfacecomponent that is present on an outer surface of the housing forming theprimary unit 104. The input control can be used to control aspects ofthe function of the device 100. For example, the input control can beused to power the device off and on or turn the electrical stimulationoff and on. Other functions are also possible. For example, the inputcontrol can be used to control wireless transmissivity. In someembodiments, the device can include more than one input control 106. Forexample, the device 100 can include two, three, four, or more inputcontrols 106. In some embodiments, the device 100 does not include aninput control 106. In some embodiments, the input control is positionedgenerally in the middle of the device 100. The input control 106 may bepositioned elsewhere on the device, for example on a side of the device100. In general, the device may have a thickness 150 that is relativelythin (e.g., less than 30 mm).

FIG. 2A shows a lightweight and wearable apparatus that includes aprimary unit 104 with a primary electrode portion 108 and a secondaryunit 210 with a secondary electrode portion 110 positioned adjacent tothe primary unit 104. The cover 102 visible in FIGS. 1A and 1B has beenremoved to show the secondary unit held stored with the primary unit; acable (not visible in FIG. 2A) connects the secondary unit to the restof the apparatus.

FIG. 2B is a side perspective view of the apparatus of FIG. 2A. In FIG.2C the secondary unit 210 has been separated from the primary unit 104,and the two units are connected by a cable 220. Thus, the two units maybe separately positioned.

The primary unit and the secondary unit may both include a transdermalelectrode for delivery of current to the subject to evoke a cognitiveresponse. In FIGS. 2A-2C the electrodes are not visible as a removablecover 233, 233′ (e.g., covering an adhesive layer) covers the contactsurfaces of both units. The cable may be stored (e.g., wound) withineither the primary or secondary units. In the example of FIGS. 2A-2C thecable is stored within the secondary unit (not visible in FIGS. 2A-2C).

FIG. 3A shows the primary electrode portion 108 of the apparatus ofFIGS. 1A-2C. The primary electrode portion 108 comprises a cover 233′(e.g., an adhesive peel layer). Beneath the peel layer is the primaryelectrode 114 region. An adhesive (e.g., electrically conductiveadhesive) may be positioned between the cover and an electrode base 116.The primary electrode portion 108 may also include a connector 118 (e.g.electrode connector) which can be used for attaching to and deliveringcurrent processor portion of the primary unit not shown in FIG. 3A). Theelectrode contact 144 for the primary electrode region 114 is shown inthe partially transparent view of FIGS. 3B and 3C. FIG. 3B shows theprimary unit housing 155 which may enclose the processor/controller ofthe primary unit as well as the power source (e.g., a pair of batteriesin this example), as well as any additional and/or optional componentsincluding a wireless communications module. The housing also includesthe one more controls and/or one or more indicators (e.g., LEDs) thatmay be present on the surface of the housing. FIG. 3C shows the primaryunit with the housing removed, revealing a pair of batteries 334, 336, awireless module 347 (e.g., Bluetooth) and circuitry (printed circuitboards) 357, 359 for controlling the power supply and generating andconditioning the current waveforms applied between the electrode in theprimary unit and the electrode in the secondary unit.

The primary electrode region 114 region is configured to be positionedagainst the skin of a user during a stimulation session. The top surfaceof the electrode 114 region shown in FIG. 3A is the surface configuredto be positioned on the skin of a user. As described below, the primaryelectrode region can be adhered to the skin or can be held in place byan accessory or other article.

The primary electrode 114 region shown in FIG. 3A is a transdermaladhesive electrode. The adhesive can be one of a variety of adhesives,for example pressure sensitive adhesives and dissolvable adhesives. Theadhesive can be electrically conductive. Some examples of adhesivelayers include acrylics (e.g., cyanoacrylate), silicone, polyurethane,and bio adhesives. The peel layer 233′ can be used to maintain theadhesive properties of the electrode 114 when the device 100 is notbeing used. Embodiments of adhesives are described in more detail below.In some embodiments, the primary electrode 108 does not include anadhesive layer. In these embodiments, the primary electrode can be heldagainst the skin of a user using a different technique. For example, thesubject may wear an item configured to hold the electrode against theskin. In some embodiments, the subject wears a wrap or headbandconfigured to hold the primary electrode against the skin. Otheraccessories and articles are also possible. For example, in someembodiments, a user uses a hat or glasses to hold the electrode inplace. For example a glasses-like article can be used to hold anelectrode over an ear of a user.

The primary electrode portion 108 may be foiined integrally with theprimary unit 104. In some embodiments, the primary electrode portion canbe configured as a cartridge, to be detachably coupled to the primaryunit 104 using the connector 118. In some embodiments, the primaryand/or secondary electrode portion is disposable and can be used for acertain period of time, and can then be replaced with another primaryelectrode portion. The term ‘disposable’ can refer to the portion beingused a number of times (e.g., 1-10, 10-25, 25-50, >50) and then beingthrown away. In some embodiments, the portion is not thrown away, but isrefurbished to be able to be used again. The term disposable isdescribed in further detail herein.

The primary electrode base 116 is configured to be positioned within theprimary unit 104. The primary electrode base 116 can comprise a bottomsurface configured to mate with an inner surface of the primary unit104. The connector 118 is a snap connector, but other configurations arealso possible. For example, the connector can comprise a latch,screw-on, or micro-snap configuration. The connector 118 can provideboth a physical and electrical connection between the primary electrode114 and the primary unit 104. In some embodiments, the primary electrodeportion 108 can include one or more electrical connectors and one ormore separate physical connectors.

FIGS. 4A and 4B illustrates one variation of a secondary electrodeportion 110 of a secondary unit such as the one shown in FIGS. 2A-2C.The secondary electrode portion 110 shown in FIG. 4A includes a peellayer 233. The peel layer 233 can be similar to the peel layer 233′described with respect to FIGS. 3A-3C. Beneath the peel layer 120 ispositioned the secondary electrode region 122, including an electrode(secondary electrode) 422. A secondary electrode base 124 is positionedbeneath the secondary electrode 122. A secondary electrode cover 126 ispositioned beneath the secondary electrode base 124.

In FIG. 4B the secondary unit has been made partially transparent toillustrate the internal elements, including an electrode 422 and cable128. The cable is arranged within the layer formed by the secondary unitand may be extended from the secondary unit by pulling the secondaryunit away from the primary unit.

As illustrated above in FIG. 2C, the secondary electrode portion 110 canbe configured to be detached from the primary unit 104 and positionedagainst the skin (e.g., on the skin, on the hair, on the ear, etc.) of auser. The top surface of the secondary electrode, as viewed in FIG. 4Ais configured to be positioned against the skin of a user. Similar tothe primary electrode region 114, the secondary electrode region 122 canbe adhered to the skin or can be held in place by an accessory or otherarticle.

The secondary electrode region 122 may include a transdermal adhesive(which may be conductive) for coupling the electrode to the subject. Theadhesive can be one of a variety of adhesives, for example pressuresensitive adhesives and dissolvable adhesives. The adhesive can beelectrically conductive. Some examples of adhesive layers includeacrylics (e.g., cyanoacrylate), silicone, polyurethane and bioadhesives. The peel layer 233 can be used to maintain the adhesiveproperties of the electrode region 122 when the device 100 is not beingused. In some embodiments, the secondary electrode region 122 is notadhesive. In these embodiments, the primary electrode region can be heldagainst the skin of a user using a different method. For example, thesubject may wear an item configured to hold the electrode against theskin. In some embodiments, the subject wears a wrap or headbandconfigured to hold the primary electrode region against the skin.

The secondary electrode base and cover 124, 126 can provide protectionto the secondary electrode. The base 124, 126 can also provide packagingfor the secondary electrode portion 110, for example when sold as aseparate unit or cartridge. The base 124 and cover 126 can also beconfigured to hold the cable 128, as described with respect to FIGS. 4Band 4C. In some embodiments, the secondary electrode region 122 isconnected to the primary electrode portion 108 or primary unit 104 usinga connector (e.g., similar to connector 118) positioned at the secondaryelectrode base 124 and/or cover. In some embodiments, the secondaryelectrode 122, base 124, or cover 126 includes an adhesive that can beused to attach the secondary electrode portion 110 to the primaryelectrode portion 108. In some embodiments, the secondary electrodeportion 110 can be held in place within the keeper 104 by a cover suchas that shown in FIGS. 1A and 1B.

The secondary electrode portion 110 can be configured as a cartridge, tobe detachably coupled to the primary unit 104 and/or the primaryelectrode portion 108 using a connector, adhesive, or the like. In someembodiments, the secondary electrode portion is disposable and can beused for a certain period of time, and can then be replaced with anotheror the same secondary electrode portion 110, as described with respectto the primary electrode portion 108 above.

FIG. 4C illustrates a bottom perspective view of the secondary electrodeportion 110 with the cover 126 removed. The second electrode base 124has a recessed portion sized to fit the cable 128 that connects thesecond electrode portion 110 to the primary unit 104 via connector 129.The cable 128 is shown furled within the base 124 in FIGS. 4B and 4C. Insome embodiments, the furled cable 128 can serve to connect the twoelectrode portions 108, 110. In some embodiments, the base 124 will notinclude a recessed portion for the cable 128. The cable 128 can includeone of a variety of wires, including a multicore cable (e.g., copperwire, carbon nanotube wire), a flexible flat wire (e.g., a ribboncable), and the like. In some embodiments, the cable 128 can include aset of more than one wire or cable.

FIG. 5A illustrates the interior of an embodiment of the housing (keeper104) of the primary unit, as described above in reference to FIGS.3A-3C. The keeper may include a housing 130 that serves as a base forthe keeper 104. Situated within the housing 130 is a two-part PCBcontroller 136. In some embodiments, the controller 136 may have feweror more than two parts. The parts may be oriented differently than theconfiguration shown in FIG. 5. The controller 136 can be configured todrive stimulation between the primary electrode 114 and the secondaryelectrode 122 when the electrodes 114, 122 are electrically connected.The controller 136 can be configured to drive stimulation based on anumber of parameters, including current amplitude, current frequency,pulse width, pulse duration, pulse frequency, pulse waveform, burstduration, burst frequency, off-time, burst waveform, positive dutycycle, negative duty cycle, and on/off. Other parameters can also beutilized. For example, the controller can be configured to drivestimulation in which no current is provided between pulses or in whichthe current is short-circuited through a resistor between pulses (forinstance, to provide sharper pulse boundaries due to reduction ofcapacitive current in the circuit). The controller 136 can utilize acurrent generator to drive stimulation. Other devices are also possible.For example, the controller 136 can utilize a voltage generator in someembodiments. A current generator or other similar device may be part ofthe controller 136. In some embodiments the current or voltage generatoris positioned within the primary unit, but is not part of the controller136. As described in further detail below, in some embodiments, thestimulation driven by the controller can depend on data received fromitems contained within or without the device 100. For example,measurements taken by devices such as impedance meters or physiologicalsensors can influence the stimulation provided. In some embodiments, thecontroller is configured to adjust current across the primary andsecondary electrodes based on a detected impedance. In some embodiments,the stimulation can be triggered or controlled wirelessly from a remotedevice such as a smartphone.

In FIG. 5A two batteries 134 covered by doors 132 are illustrated. Insome embodiments, the keeper 104 will not include doors 132 for thebatteries 134. In some embodiments, one battery supply is configured toprovide power to the electrodes while a second battery supply may beconfigured to provide power for stimulation delivered to controlcomponents and other components of the device (e.g., LED indicator orinternal clock). In this manner, both the advantages of limitations ondevice usage can be achieved while maintaining convenience of having areusable portion of the device that requires less maintenance in betweenuses. Certain embodiments may provide a battery supply integrated intothe main housing of the device, while a second battery supply for theelectrodes could be contained within a disposable portion of the device.In some embodiments, the device 100 comprises one battery. In someembodiments, the device 100 comprises more than two batteries. Forexample, the device 100 can comprise three batteries.

In some embodiments, coin cell batteries can be used. Other types ofbatteries are also possible. For example, in some embodiments, buttoncells can be used. An example of a suitable battery is the EnergizerCR1220 lithium coin battery. Other possibilities include the CR 1025 andthe CR1216. The CR1025 has enough power to delivery 1 mA for about 30minutes (0.5 mAh). The CR1216 lithium coin battery is even smaller:about 0.5 inch round, 20^(th) inch high. These and other battery foamfactors can be advantageous for a disposable, limited use or single usesystem. Advantageously, usage of the device can be limited as to notallow a user to overuse or forget to turn off the device.

In some embodiments, a chain of batteries in series is used to generatehigher voltages required for stimulation. For example, six 1.5Vbatteries in series can be used to create a 9V source. In someembodiments, transformer or buck-boost strategies are used to generatehigher voltages from a low voltage battery source. One of ordinary skillin the art would appreciate that there are numerous strategies forgenerating higher voltages from lower voltage sources.

In some embodiments of the invention, the battery is charged by one ormore solar panels or by harvesting energy from the movements of a userfor example by using piezopolymers or piezoelectric fiber composites asdisclosed in International Patent Application No. PCT/US2010/055527(Publication No. WO/2011/057028) titled “DEVICES AND METHODS FORMODULATING BRAIN ACTIVITY” by inventor Tyler).

FIG. 5B depicts a side view of the primary unit 104 without the housing130. This example includes a wireless communications module 140positioned near one of the controller 136 components. The wirelesscommunications module 140 can be configured to transmit informationusing one or more wireless modes such as Bluetooth, Wi-Fi, cellular datasignals, or another form of wireless communication. In this manner, aremote server can trigger electrical stimulation via the Internet orother local or wide area network means, or a PC, laptop, smartphone, ortablet. Such wirelessly connected devices can be used to remotelycontrol parameters of electrical stimulation (e.g., current amplitude,current frequency, pulse width, pulse duration, pulse frequency, pulsewaveform, burst duration, burst frequency, off-time, burst waveform,positive duty cycle, negative duty cycle, and on/off). In someembodiments, the device is not configured to control parameters ofelectrical stimulation, such as those described above. In suchembodiments, the device may advantageously be smaller as less room maybe used for device circuitry.

The device 100 is shown as having a generally rectangular shape withrounded edges. In some embodiments, the primary unit 104 can have adifferent shape. For example, the primary unit 104 can have a generallyovular, rectangular, or circular shape.

The device 100 is shown as having a generally kidney bean-shapedprofile, as seen from the view depicted in FIG. 1B. In some embodiments,the device has a differently shaped profile. For example, the profilecan be generally rectangular, generally trapezoidal or generally ovular.The profile can have rounded edges or generally sharp edges. In somevariations (as illustrated, the outer subject-contacting surface of theprimary and secondary units is contoured to better fit the subject'shead. For example, as illustrated, the primary and secondary unitsubject-contacting surfaces are curved slightly (bowed inward) to betterfit the subject's head or neck. In addition, these surfaces may beflexible, bendable or otherwise configured to contour to the shape ofthe subject. Thus, in general the primary and secondary units may besufficiently curved, bendable, or flexible to conform to the shape ofthe subject's body where the primary and secondary units are coupled(and particularly where the electrode regions contact the subject'sskin).

FIG. 26 is a schematic illustration of a lightweight, wearable andself-contained electrical stimulation apparatus that illustrates bothdurable (“reusable”) 2601 and disposable components 2603. In FIG. 26,the reusable assembly may include a processor (e.g., programmablemicrocontroller 2605, and programming interface 2607). The reusablecomponents may also include one or more (or all) of: one or moreindicators 2609, one or more user controls 2611, current source circuit2613 (e.g., one or more current sources 2615, connector(s) 2617, testpoint(s) 2619), and one or more impedance monitoring module 2621. Theimpedance monitoring module is typically connected to microcontroller(not shown) which may act upon it or may adjust the applied current(s)based on information received from the impedance monitoring module. Thepower source module 2603 is also typically included in the reusablehardware assembly. Although one or more batteries may be replaceable ordisposable, such power sources are typically intended for multiple uses,and may be rechargeable. In some variations, however, the power source(power supply 2631, such as batteries) may be disposable and included inthe disposable assembly 2651. The power source module may also include apower supply access 2633, the power supply (e.g., battery, capacitivepower source, etc.) 2631, a power monitor (e.g., battery voltagemonitoring module 2635), and a step-down 2637 and/or step-up converter2639.

As mentioned above, any of the apparatuses described herein may alsoinclude one or more wireless communication module 2691, which may alsobe part of the durable assembly. For example, a wireless communicationmodule may include an antenna, encoder, D/A processor, filters,amplifiers, etc. The wireless communication module may be duplex(half-duplex, full-duplex, etc.) for both receiving and transmittinginformation. The durable/reusable assembly 2601 may also include amemory (not shown) for storing instructions and/or performanceinformation about the apparatus; the memory may be coupled to either orboth the controller/processor 2605 and the wireless communication module2691.

Embodiments of methods of using a lightweight and wearable apparatus forinducing a cognitive effect will now be described. In some embodiments,a subject using the device or third party will detach the secondaryelectrode portion 110 from the primary unit, separating the twoelectrode portions, prior to initiating a stimulation session. In someembodiments, the primary electrode portion 108 and secondary electrodeportion 110 are not positioned within the primary unit 104. In suchembodiments, the user or third party can insert the first electrodeportion (e.g., a replaceable or disposable cartridge) into the primaryunit 104 (e.g., using snap 118). In some embodiments, the user or thirdparty inserts the primary electrode portion 108 and secondary electrodeportion 110 (e.g., as a replaceable or disposable cartridge) into theprimary unit 104, and then detaches the secondary electrode portion 110from the primary unit 104.

The user or third party can position the primary unit 104 including theprimary electrode portion 108 at a first location on a user and positionthe secondary electrode portion 110 at a second location on a user. Insome embodiments, one or both of the primary and secondary electrodeportions 108, 110 are positioned on the head of a user. In someembodiments, one or both of the primary and secondary electrode portions108, 110 are positioned on the neck of a user. For example, the primaryelectrode portion 108 can be positioned on the forehead of a user andthe secondary electrode portion 110 can be positioned on a neck of auser. In some embodiments, one or both of the primary and secondaryelectrode portions 108, 110 is positioned on the periphery of a user(e.g., locations other than the head or neck). As described above, theelectrode portions can be adhered to the skin of a user or worn using anaccessory or article.

The secondary electrode portion 110 can be electrically connected to theprimary electrode portion 108 by using the cable 128 and connector 129either before or after positioning the electrode portions 108, 110 onthe skin. In some embodiments the two electrode portions may already beconnected. Once the two electrode portions 108, 110 are electricallyconnected, the user can drive stimulation between the electrodes 114,122. As described above, the stimulation can be driven based onpredetermined parameters. In some embodiments, a user can control thestimulation driven using the input control. In some embodiments, thedevice receives stimulation parameters wirelessly. In some embodiments,a user or third party can control the stimulation parameters on aseparate device such as a smartphone, laptop, tablet, etc., and cantransmit the parameters to the device 100 using a wired or wirelessconnection.

As described above, the device 100 includes a modular secondaryelectrode portion 110 that can be attached to the primary unit 104. Insome embodiments, the device 100 includes more than one secondaryelectrode portion. Each secondary electrode portion can have its ownadherent pad and one or more electrodes as well as a connection meansallowing for connection (e.g., wired, wireless) to the primary unit 104.The multiple electrode portions can be arranged in an array with shapesincluding: round, elliptical, triangular, square, rectangular,trapezoidal, polygonal, oblong, horseshoe-shaped, hooked, orirregularly-shaped. In some embodiments, the secondary portion 110 canbe attached to the primary portion 108 via a flexible wire, as describedabove. In these embodiments, power and control signals can be sent byway of the flexible wire. In other embodiments, the secondary unitsinclude an independent power source (e.g., battery) and receive controlsignals from the primary unit via the connection means either wirelessly(e.g., Bluetooth Low Energy) or through a wired connection (e.g.,flexible wiring extending from the primary unit).

In some embodiments, an indicator communicates to the user (and/or athird party) that electrical stimulation is underway. In an embodimentof the invention, an indicator communicates to the user (and/or a thirdparty) that electrical stimulation will end in a certain amount of time.In an embodiment of the invention, an indicator communicates to the user(and/or a third party) that electrical stimulation will begin soon.

In embodiments wherein an indicator communicates to the user, theindicator can take the form of an LED or other visual stimulus;transducer, buzzer, or other tactile transducer; a speaker orskull-coupled transducer for transmitting vibration that can be detectedas an auditory stimulus; an emitted chemical signal detected as anolfactory or gustatory signal by the user; or a signal transmitted viaan application used by the subject on a PC, laptop, tablet, smartphone,or other mobile computing device.

In some embodiments, the recipient of electrical stimulation triggerstheir own electrical stimulation. In alternative embodiments, a thirdparty triggers electrical stimulation.

In embodiments of the invention, one or more of the electrodes is a dryelectrode. In some embodiments that incorporate one or more dryelectrodes, the dry electrodes are designed to have finger-likeprojections useful for contacting the skull through hair and composed ofa material chosen from the group of: fabric, foam, rubber, or anothermaterial or materials known to one skilled in the art of creating dryelectrodes.

As described above, the electrical stimulation device can includedisposable components. In some embodiments, the entire assembly isdisposable. In some embodiments, the device is composed of separablenon-disposable and disposable components. For example, the primary unit104 may be non-disposable, while the first and second electrode portions108, 110 can be disposable. In this manner, robust and reusablecomponents of the system can be reused, saving resources and reducingcost, while permitting the replacement of other components such assingle-use (or limited use) electrodes (which may not reliably adhere tothe head after a single use) or a battery.

In some embodiments, the system is configured to be a “single use”system that is only used once and then disposed. In other embodiments,the system is configured to be disposable after a certain number of usesand is thus referred to as “multiple use”. In some embodiments, thesystem is configured to be disposed after a number of uses within arange. In alternative embodiments of the invention, the system isconfigured to be disposed after a fixed number of uses chosen from thegroup of: more than once, more than twice, more than 3 times, more than4 times, more than 5 times, more than 10 times, more than 25 times, morethan 50 times, more than 100 times, more than 1000 times, or more than10000 times. In alternative embodiments of the invention, the system isconfigured to be disposed after a fixed period of time of use chosenfrom the group of: more than 10 seconds, more than 30 seconds, more than1 minute, more than 2 minutes, more than 3 minutes, more than 4 minutes,more than 5 minutes, more than 7 minutes, more than 10 minutes, morethan 15 minutes, more than 30 minutes, more than 45 minutes, more than 1hour, more than 2 hours, more than 3 hours, more than 5 hours, more than10 hours, more than 20 hours, or longer. In an embodiment of theinvention, a fixed-use fuse, burnout circuit, limited battery, or otherelectronic or mechanical system is used to cease device operation oncethe limit in uses or time has been reached. In an embodiment of theinvention, a machine readable memory is used to count the number of usesor length of time a disposable device or system component has been used,then a microcontroller or other electrical component compares the valuein memory to a maximum number of uses or length of time to determinewhether stimulation is triggered by the system. In some embodiments, aradiofrequency identification (RFID) tag is a component of a disposablecomponent of a stimulation device and configured to make certain thatthe disposable component is not used more often or for longer thanintended. The number of uses and/or length of use is transmittedwirelessly to a PC, laptop, smartphone, tablet, or other mobilecomputing device.

In some embodiments in which the stimulation device is configured to besemi-disposable, reusable components integrated into a main housing canbe permanently used for all sessions of stimulation. In someembodiments, the reusable components incorporated into the main housingcan be designed for re-use a number of times chosen from the group of:more than once, more than twice, more than 3 times, more than 4 times,more than 5 times, more than 10 times, more than 25 times, more than 50times, more than 100 times, more than 1000 times, or more than 10000times.

In some embodiments in which the stimulation device is configured to besemi-disposable, the disposable portion includes one or more electrodes.In some embodiments in which the stimulation device is configured to besemi-disposable, the disposable portion includes a battery. In someembodiments in which the stimulation device is configured to besemi-disposable, the disposable portion includes an electricalconnector. In some embodiments in which the stimulation device isconfigured to be semi-disposable, the disposable portion includes anelectrically conductive adhesive. In some embodiments in which thestimulation device is configured to be semi-disposable, the disposableportion includes a fuse or limiting switch configured to terminate (orburn out in the case of a fuse) after exceeding a desired time orcurrent level, protecting the user from over use or undesirable currentsurges or fluctuations (e.g., permitting use without the need to havepredefined range for the stimulation). In some embodiments in which thestimulation device is configured to be semi-disposable, the disposableportion includes a microcontroller. In some embodiments in which thestimulation device is configured to be semi-disposable, the disposableportion includes a user interface component. In some embodiments inwhich the stimulation device is configured to be semi-disposable, thedisposable portion includes packaging, a tactile transducer, a speaker,or an LED. One of ordinary skill in the art will appreciate that thevarious elements of the disposable portions of the stimulation deviceare not necessarily a single disposable component. For example, in someembodiments, the disposable portion may be two or more separatecomponents, such as a disposable contact pad, comprising an adherent andone or more electrodes, while a disposable battery may be detachablyintegrated within a semi-disposable or non-disposable portion of thedevice (e.g., battery compartment).

In some embodiments, a disposable stimulation device or disposableportion of a stimulation device is configured to be returned to thecompany or a third party for recycling. In an embodiment of theinvention, a refund is provided for a disposable system returned by auser. One or more new disposable systems may be provided to a user orsent to them as a replacement for a returned or disposed of disposablestimulation device component. In some embodiments, return packaging isprovided for the user to mail a used system or used component of asystem. Users can subscribe to receive disposable stimulation devices orcomponents of stimulation devices and/or disposable portions ofstimulation devices regularly or when they have used previously receivedsystems. Embodiments incorporating recycling can be advantageous,because they may benefit the environment, particularly with respect tobatteries or other electrical components that may be toxic if disposedof improperly.

In some embodiments, the device is configured to be user-actuated and/orautomated. In this manner, embodiments of the present invention may beutilized without the need to have a skilled practitioner (e.g., medicaltechnician) available in order to oversee the placement, control andoperation of the electrical stimulation.

The above features of embodiments of stimulation devices provided hereindiffer from existing TES systems and offer key advantages for thewidespread, portable use of TES systems, including:

1) Single use or limited use electrodes that adhere to the skin, hair,face, or head can simplify system design by reducing requirements forrobustness of the electrode itself, as well as its properties withrespect to adherence to the head, electrical conductivity, andeffectiveness of stimulation.

2) Smaller, lighter, and structurally flexible form factor can enableusers to undertake normal, daily activities throughout stimulationsessions and make the device more comfortable and convenient to use.

3) Electrical, structural, and energy-storage components can be designedto lower tolerances and need not achieve long-term performance,permitting significantly reduced product pricing relative to existingTES systems (e.g., 5-10× less), significantly expanding their use andreducing the barrier to adoption versus traditional devices.

4) By eliminating the requirement for field support for hardware or longterm performance requirements customer satisfaction can be improvedwhile also lowering operational costs to maintain working products inthe field.

As described above, the device components (e.g., the first and secondelectrode portions) can include adhesive to make them self-adhering(e.g., adherent) to the skin, skull, face, hair, neck or other portionsof the head or body. The adhesive can be reversibly self-adhering. Aftera user session, the self-adhering components (for instance adhesive) canbe manually removed by the user by exerting a small amount of force. Insome embodiments, the device is designed so that little or no hair isremoved during device removal if the adhesive portion of the device wasplaced over an area with hair. In some embodiments, the adhesion isstronger and removal requires more force (e.g., similar to band aidremoval).

Adhesive used can include hydrogel, acrylic conductive adhesive, and PIB(polyisobutylene) synthetic rubber conductive adhesive. A hydrogel usedas an adhesive is soft conformable gel material that enables intimatecontact and can be ionically conductive. However, hydrogels can providea weak skin bond. Appropriate hydrogels can be manufactured by CoriumInternational and other vendors. An example of an acrylic conductiveadhesive are the EC-2 products which have been used for defibrillatorpads and EKG sensors for use over minutes to hours. Adhesives ResearchInc. is a provider of acrylic conductive adhesive. PIB (polyisobutylene)synthetic rubber conductive adhesive are designed for direct skincontact and electrical pulse applications with long term exposure (daysto weeks). PIB adhesives can be tailored to be removable or high bond.One of ordinary skill in the art will appreciate that there are numerouspressure sensitive adhesives and hydrogels that could be used withembodiments of the present invention, and embodiments of the presentinvention are contemplated for use with any type of pressure sensitiveadhesive and/or hydrogel. Particular adhesives can be chosen for their,adhesive strength, electrical conductivity, the amount of residue theyleave behind (e.g., little or none), and force required forremovability.

In some embodiments, the adhesive includes a suction device, or anothersystem that adheres the device to the head. The self-adhering propertyof at least some components of the device can advantageously hold thedevice components in place at a fixed location on the head or neck fortargeting a specific brain region. The self-adhering property of atleast some components of the device can also advantageously provide amore desirable aesthetic effect than other devices that need to beattached or worn using intrusive articles.

In some embodiments, the device is less than about 8 oz. or about 226.8g. In some embodiments, the device is less than about 7 oz or about198.4 g. In some embodiments, the device is less than about 6 oz. orabout 170.1 g. In some embodiments, the device is less than about 5 oz.or about 141.7 g. In some embodiments, the device is less than about 4oz. or about 113.4 g. In some embodiments, the device is less than about3 oz. or about 85.0 g. In some embodiments, the device is between about1 oz. and about 2 oz., or between about 28.3 g. and about 56.7 g. Forexample, the device can be about 1.25 oz. or about 35.4 g. In someembodiments, the device is less than about 1 oz. or 28.3 g. In someembodiments, the device is less than about 0.5 oz. or about 14.2 g. Forexample, the device can be about 0.25 oz. or about 7 g. A sufficientlylow weight can aid in allowing the device to be self-adhering. In someembodiments, the device may not be sufficiently light to beself-adhering. A lightweight device may also increase comfort, reducecost, and reduce the area of electrical stimulation on the scalp and/orin the brain in order to achieve tighter focusing of the inducedelectric field in the brain.

The electrical stimulation device can be configured for conformabilityto the head, face, neck, or other body region. In some embodiments, thedevice components are flexible. In some embodiments, all componentslarger than the curvature of the target body area are made of flexiblematerials. In some embodiments, flexible mechanical elements betweeninflexible components permit conformability to the body.

In some embodiments, the device long axis dimension is less than about30 cm, less than about 20 cm, less than about 12 cm, less than about 10cm, less than about 9 cm, less than about 8 cm, less than about 7 cm,less than about 6 cm, less than about 5 cm, less than about 4 cm, lessthan about 3 cm, less than about 2 cm, or less than about 1 cm.

In some embodiments, the device has a diameter of less than about 12 cm,less than about 10 cm, less than about 9 cm, less than about 8 cm, lessthan about 7 cm, less than about 6 cm, less than about 5 cm, less thanabout 4 cm, less than about 3 cm, less than about 2 cm, or less thanabout 1 cm.

In some embodiments, the device has a height or profile of less thanabout 30 cm, less than about 20 cm, less than about 30 mm, less thanabout 20 mm, less than about 10 mm, less than about 9 mm, less thanabout 8 mm, less than about 7 mm, less than about 6 mm, less than about5 mm, less than about 4 mm, less than about 3 cm, less than about 2 mm,or less than about 1 mm. A low-profile device may advantageously havebetter adhesion properties than a larger-profile device. For example,its center of mass is closer to the adhesive at the user's skin.

In one embodiment, the footprint of the device is less than about 5 cmin diameter and less than about 0.625 cm in height and weighs less thanabout 2 ounces (or about 56.7 g). In some embodiments, the footprint ofthe device is less than about 3.75 cm in diameter and less than about0.3 cm in height and weighs less than about 1 ounce (or about 28.3 g).

In alternative embodiments, the configuration of the device providesphysical stability. For instance, a wrap-around-the-ear configurationcan provide additional support for a TES assembly by transferring weightto the ear (FIG. 14B).

In some embodiments, the electrical stimulation device does not includeuser controllable elements for adjusting parameters of stimulation. Insuch embodiments, pre-determined stimulation protocols can be chosen forsafety and efficacy and be stored in computer readable memory present inthe device. The pre-determined setting can be triggered by toggling theon/off switch. The settings can also be triggered when the system sensesa low impedance connection between electrodes occurring for instancewhen electrodes have been conductively adhered to a user's skin. In someembodiments, user controllable elements for adjusting parameters ofstimulation can be located remotely from the device for example on asmartphone, computer, or other mobile computing device. In someembodiments, the device does not require user input concerning the timeof stimulation, intensity of stimulation, frequency of stimulation, orother stimulation parameter.

In some embodiments, a GPS antenna, RFID tag, Bluetooth transmitter,Wi-Fi transmitter, and/or other wireless communication system are usedfor transmitting to and from the electrical stimulation device. In someembodiments, wireless communication is used to trigger electricalstimulation remotely or due to the presence of the device in aparticular location. For example, a user may wear an electricalstimulation device configured for improved learning that is onlytriggered when they are in a classroom and a lecture has begun. Inanother embodiment, a device configured to improve motor learning andmotor performance is worn by a golfer and activated when the subject isin proximity to their golf club.

As described above, transdermal electrical stimulation can include TES.TES can include transcranial direct current stimulation (tDCS),transcranial alternating current stimulation (tACS), cranialelectrotherapy stimulation (CES), and transcranial random noisestimulation (tRNS). Unlike other forms of energy that can be transmittedtransdermally or transcranially such as ultrasound, transmission of anelectrical field in the brain occurs at the speed of light and is thusinstantaneous on biological timescales.

In some embodiments, the device incorporates a built-in impedance meter.Impedance meters can advantageously provide the user with feedback aboutthe impedance of each electrode (or electrode pair) to guide the user orother individual as to the effectiveness with which an electrode hasbeen electrically coupled to their head. In various embodiments of theinvention, feedback about electrode impedance is provided through one ormore of: a graphical user interface (i.e. one presented on the screen ofa mobile computing device), one or more indicator lights, or other userinterface or control unit. In an embodiment of the invention, feedbackto the user about the impedance is designed to inform the user to adjusta stimulation device to couple it more firmly to the body and thusreduce impedance. In an embodiment of the invention, feedback to theuser about the impedance is designed to inform the user if a shortcircuit is present (i.e. that the impedance is too low) so that the usercan resolve the short circuit (e.g. dry their head if it is raining). Inan embodiment of the invention that uses dry electrodes, the device isconfigured to adjust, pause, or otherwise modulate stimulation due tocapacitive interference as is known to occur for dry electrodes duringmovement such as raising a hand near the head.

Lower impedance between electrodes can indicate conductance via thehead, scalp, face, or other body part of the user. In an embodiment, thedevice is engineered to automatically trigger electrical stimulationwhen the impedance between one or more pairs of electrodes falls below athreshold value. In other embodiments, the device is engineered suchthat impedance is determined upon an event (e.g., toggling of an on/offswitch) in order to verify sufficient contact with the skin of a userprior to engaging stimulation. In an embodiment, the device isengineered to gate electrical stimulation so that it only occurs whenthe impedance between one or more pairs of electrodes falls below athreshold value chosen from the group of: less than about 250 kΩ, lessthan about 100 kΩ, less than about 50 kΩ, less than about 25 kΩ, lessthan about 10 kΩ, less than about 5 kΩ, or less than about 1 kΩ. In anembodiment, the device is engineered to gate electrical stimulation soit only occurs when the impedance between one or more pairs ofelectrodes exceeds a threshold value to confirm that no electricalshorts are present (e.g. due to rain or wet hair) and the thresholdvalue is chosen from the group of: greater than about 1Ω, greater thanabout 5Ω, greater than about 10Ω, greater than about 50Ω, greater thanabout 100Ω, or greater than about 500Ω. In some embodiments, thestimulation driven by the controller is influenced by the impedancemeasured (e.g. at least one of current amplitude, current frequency,pulse width, pulse duration, pulse frequency, pulse waveform, burstduration, burst frequency, off-time, burst waveform, positive dutycycle, negative duty cycle, and on/off).

The device can be configured to deliver alternating current (AC), directcurrent (DC), or a combination of alternating and direct current. Insome embodiments in which the device is configured to deliveralternating current, alone or in combination with direct current, thewaveform of the alternating current is chosen from the group of sine,square, sawtooth, triangle, and other waveform, including composite,complex, and stochastic waveforms.

In some embodiments, the device is configured deliver current at one ormore frequencies between about 0.01 Hz and about 20 kHz. In someembodiments, the device is configured to deliver current at betweenabout 400 Hz and about 20 kHz. In some embodiments, the device isconfigured to deliver current at between about 650 Hz and about 20 kHz.In some embodiments, the device is configured to deliver current atbetween about 500 Hz and about 10 kHz. In some embodiments, the deviceis configured to deliver current at between about 650 Hz and about 10kHz. In particular, any of the apparatuses and methods of using themdescribed herein may include a peak power that is within a frequencyband between any of these ranges (e.g., peak power in the range of 650Hz and about 20 kHz, etc.). Thus, a primary frequency component for theapplied power (e.g., current) may be within the range, for example, ofabout 650 Hz to about 20 kHz (e.g., 650 Hz to about 10 kHz, etc.). Thisprimary frequency component may be greater than other frequencycomponents of the signal, as determined by a frequency domain (e.g.,Fourier) analysis. In some variations, the primary frequency componentis the first (principle) frequency component, having the greatest power,compared to any other frequency component of the applied signal (e.g.,in some variations, by an order of magnitude).

Particularly advantageous frequencies for tACS are at frequencies ofbrain rhythms that naturally occur between about 0.5 Hz and about 130Hz. In embodiments of the electrical stimulation device, higherfrequencies between 1 kHz and 10 kHz are used to modulate neuronalfunction. In some embodiments of the invention, the components of thesystem that deliver alternating current stimulation are configured todeliver time-varying patterns of electrical stimulation with one or moredominant frequencies at a biologically relevant range of between about0.01 Hz and about 500 Hz.

Skin irritation can be much less for AC or RNS than for DC stimulation,permitting higher current intensities without discomfort. In commonembodiments of the invention, the current delivered through a singlepair of electrodes is chosen from the group of: less than about 10 mA,less than about 5 mA, less than about 4 mA, less than about 3 mA, lessthan about 2 mA, less than about 1 mA, less than about 0.5 mA, less thanabout 0.25 mA, less than about 0.1 mA. In some embodiments of theinvention, the sum of currents transmitted by all or a subset ofelectrodes is limited to a maximum instantaneous level chosen from thegroup of: less than about 10 mA, less than about 5 mA, less than about 4mA, less than about 3 mA, less than about 2 mA, less than about 1 mA,less than about 0.5 mA, less than about 0.25 mA, less than about 0.1 mA,One of ordinary skill in the art would appreciate that there arenumerous current levels that could be utilized with embodiments of thepresent invention, and embodiments of the present invention arecontemplated for use with any appropriate level of current. Particularlyadvantageous stimulation protocols have a minimum peak current amplitudeof 2 mA.

In some embodiments, the maximum current level permitted for a singlepair of electrodes or group of electrodes is an average or cumulativevalue over a period of time chosen from the group of: less than about100 minutes; less than about 30 minutes; less than about 10 minutes;less than about 5 minutes; less than about 2 minutes; less than about 1minute; less than about 30 seconds; less than about 10 seconds; lessthan about 5 seconds; less than about 2 seconds; less than about 1seconds; less than about 300 milliseconds less than about 100milliseconds; less than about 50 milliseconds; less than about 10milliseconds; less than about 5 milliseconds; or less than about 1millisecond. One of ordinary skill in the art would appreciate thatthere are numerous periods of time that could be utilized withembodiments of the present invention, and embodiments of the presentinvention are contemplated for use with any period of time.

In some embodiments, the device may deliver random noise stimulation,similar to tRNS. The noise may be purely random (i.e. white noise). Insome embodiments, the noise is structured (e.g. pink noise). In someembodiments, the electrical stimulation is delivered with higher powerin the frequency band between about 100 Hz and about 640 Hz. One ofordinary skill in the art would appreciate that there are numerous typesof noise, structured or unstructured, that could be utilized withembodiments of the present invention, and embodiments of the presentinvention are contemplated for use with any type of noise.

In some embodiments, the device is configured so that the effect inducedby the stimulation is mediated at least in part by neurons. Inalternative embodiments of the invention, the device is configured sothat the effect is mediated at least in part by non-neuronal cells. Insome embodiments of the invention, the device is configured so that theinduced electric field has higher intensity in one or more targetedwhite matter tracts, nerves, or ganglia. In alternative embodiments ofthe invention, the device is configured so that the induced electricfield has higher intensity in one or more targeted regions of greymatter. In some embodiments of the invention, the directionality of oneor more electrical fields is modulated during a user's session. Inalternative embodiments of the invention, the location and/or intensityof one or more electrical fields is modulated during a user's session.

The number and placement of electrodes, along with the stimulationparameters, deteiinines the induced cognitive effect on a user. In someembodiments, multiple electrodes are used with a single currentgenerator such that there are one or more anode and cathode electrodes.In other embodiments, multiple current generators create multiplecurrent source-sink pairs to create a desired spatial pattern ofelectrical current density at one or more target sites in the brain. Invarious embodiments of the invention, the number of electrodes used ischosen from the group of: more than 2 electrodes, more than 3electrodes, more than 4 electrodes, more than 5 electrodes, more than 7electrodes, more than 10 electrodes, more than 15 electrodes, more than25 electrodes, more than 50 electrodes, more than 100 electrodes, morethan 500 electrodes, more than 1000 electrodes, more than 5000electrodes, or more than 10000 electrodes.

In some embodiments, one or more dominant frequencies of AC areindividualized for a user based on their own endogenous brain rhythms.The peak frequency for behaviorally relevant rhythms such as alpharhythms can vary by several Hz between individuals. Thus, in someembodiments of the invention, the device is configured to modulate alphaor other rhythms at the frequency observed in that user with EEG oranother form of brain recording. In an embodiment of the invention,brain rhythms are modulated by transmitted alternating currentelectrical stimulation at a similar frequency and either in phase or outof phase with an endogenous brain rhythm.

In some embodiments, one or more dominant AC frequencies are chosen suchthat electrical coupling is more effective or optimal for one or morecell types (pyramidal neurons, interneurons, glial cells, or other celltypes) based on their membrane time constants, ion channel kinetics, orother biophysical property. In other embodiments, one or more dominantAC frequencies are chosen to optimize coupling for a subcellularcompartment such as the dendrite, axon hillock, cell body, or synapse.

In some embodiments of the invention, the electrical stimulation ispulsed, as shown in FIG. 6. FIG. 6 illustrates a targeted AC stimulationprotocol involving repeated pulsing shown in waveforms 201, 202, and203. FIG. 6 also depicts the protocol duration 204 and repetition period205. As shown, the protocol repetition period is the inverse of therepetition frequency. Pulsing electrical stimulation can be an effectivestrategy for inducing a cognitive effect.

Pulsed stimulation can use AC and/or DC, as shown in FIG. 7. FIG. 7depicts a DC stimulation protocol including pulsing and repeating shownin waveforms 301, 302, 303. The protocol duration 304 is also shown. Theprotocol repetition period 305 is equal to the inverse of the repetitionfrequency. In some embodiments, the device delivers a protocol of two ormore pulses 201, 301 chosen from the group of: about more than 2 pulses,about more than 3 pulses, about more than 4 pulses, about more than 5pulses, about more than 10 pulses, about more than 20 pulses, about morethan 50 pulses, about more than 100 pulses, about more than 500 pulses,about more than 1000 pulses, about more than 10000 pulses, or morepulses. The inter-pulse time and the number of pulses can determine thestimulation protocol duration 204, 304. In some embodiments, a pulsedprotocol is repeated 202, 203, 302, 303 at a protocol repetitionfrequency 205, 305 chosen from the group of: about more than 0.001 Hz,about more than 0.01 Hz, about more than 0.1 Hz, about more than 1 Hz,about more than 5 Hz, about more than 10 Hz, about more than 20 Hz,about more than 50 Hz, about more than 100 Hz, about more than 250 Hz,about more than 500 Hz, about more than 1000 Hz, or faster. In someembodiments of the invention the pulse repetition rate is modulatedduring a user session. In some embodiments of the invention, the pulserepetition rate is specific to a subset of one or more electrodes.Different electrodes or subsets of electrodes are pulsed with differentrepetition rates. Similarly, in some embodiments different electrodes orsubsets of electrodes are driven at different frequencies and/or withdifferent amplitudes.

FIG. 8A illustrates various example waveforms. Amplitude modulatedstimulation is shown at waveforms 401, 402, 403. Frequency modulatedstimulation is shown at waveforms 404, 405, 406. Frequency and amplitudemodulated stimulation is shown at waveforms 407, 408, 409. FIG. 8Billustrates various electrode positions 411, 412, 413 arranged on a head410 of a user. The stimulation protocol 414 is used in FIG. 8B. FIG. 8Cillustrates how each pulse in the overall stimulation applied 414 comesfrom a different electrode position 411, 412, 413.

Computational models can be advantageous for modeling the transmissionof electric fields in the brain. Effective computational models accountfor differential field shaping effects of different tissue types (e.g.skin, skull, white matter, grey matter, etc.) to derive an accurateestimate of induced electric fields.

In some embodiments, two or more electrodes are configured to optionallyrecord EEG by switching appropriate electrically connected circuits. Inother embodiments, two or more EEG electrodes and electrical hardwarefor amplifying, filtering, and otherwise processing EEG signals areincorporated into the electrical stimulation device. In someembodiments, EEG electrodes and electrical hardware are contained in oneor more separate housings and further comprise wired or wireless systemsfor transmitting raw and/or processed EEG signals to an electricalstimulation device.

A finite element model (FEM) can aid in estimating electric fields inthe body, including the brain, spinal cord, and nerves (e.g. cranialnerves) and can be used to determine the number, location, size, andshape of stimulating electrodes to use for delivering current to adesired target area. The FEM also determines stimulation parameters foreach electrode (if there is a single reference electrode) or pair ofelectrodes (if multiple reference electrodes are used) in order tocreate a focused electric field in a brain region of interest. FEMmodels can be configured to optimize for both intensity and direction ofcurrent with a particular spatial and temporal profile. Both thestrength and direction of an induced electric field determine theneuromodulation that occurs. The direction of an electrical field isthought to most significantly affect neuromodulation of white matter.

FEM electric field calculations can be employed to estimate the spatialdistribution of current density in the brain for a particular electrodemontage and stimulation protocol. FEM's that use a Standard Model assumea fixed anatomy. The electric field distribution during electricalstimulation is strongly dependent on the electric tissue properties ofskin, skull, cerebrospinal fluid, and brain tissue. These anatomical andbiophysical parameters are incorporated into FEM models. To determineuseful electrode configurations and stimulation protocols, an algorithmoptimizes electrode positions and currents for a search space thatincludes one or more of: electrode positions and maximum and/or minimumcurrents at the electrodes, electrode size, and electrode shape. Theoptimization maximizes the electric field in a certain brain area andminimizes field strength at surrounding regions to achieve desiredfocality.

Recent research and disclosures have described workflows and relatedmethods for FEM of electric fields in the brain. Some of these FEMmodels have used an idealized spherical model of the head (DaSilva etal., 2011 and Tyler et al. U.S. Patent application 61/663,409), the fulldisclosures of which are incorporated herein by reference.

FIGS. 9A-E shows the results of FEM analysis, depicting common largeelectrode montage for DC stimulation and modeled fields. FIG. 9A showsStandard Model anatomy 501 and a common arrangement of two largeelectrodes (5 cm×7 cm, rectangular) placed over the motor cortex (anode)503 and orbitofrontal cortex (cathode) 502. FIG. 9B shows the electricpotential on the scalp. The magnitude of electric potential is indicatedby shading in all figure panels. The potential of the anode 505 is setto 1 Volt and the potential of the cathode 504 is set to 0 Volt. Byadjusting the potential difference between the anode and cathode anintended current strength can be achieved. FIG. 9C shows the absolutemagnitude of the electric field on the scalp. Note that the highestfield strength occurs at the edges of the electrodes 506, 507 where thegradient of the electric potential is strongest. Current gradient occursat the boundaries but not under a TES electrode, because each electrodeis at iso potential. FIG. 9D shows the absolute magnitude of theelectric field in the brain. Peak electric fields occur underneath theelectrode edges 508, 509. FIG. 9E shows the direction and magnitude ofelectric fields in the brain. The electric field is directed from theanode 511 to the cathode 510.

More focused electric fields can be achieved with electrodeconfigurations with one or more electrodes that surround a centralelectrode and are configured to pass current between the centralelectrode and the one or more surrounding electrodes. In embodiments ofthe invention, a set of cathodes surrounds a single anode. Inalternative embodiments, a set of anodes surrounds a single cathode.FIGS. 10A-10D shows the results of FEM analysis with a Standard Model601 for a triangle shaped electrode configuration. For each panel, fourcircle shaped electrodes (radius 1 cm) 602 are modeled over premotorcortex. The anode is placed in the center and the cathodes are placed inthe triangle corners. FIG. 10B shows the distribution of electricpotential on the scalp. The potential of the anode is set to 1 Volt 603and the potential of the cathodes is set to 0 Volt. By adjusting thepotential difference between the anode and cathodes current is induced.FIG. 10C shows the distribution of electric potential in the brain. Highpotentials 604 are confined to a small volume underneath the anode. FIG.10D shows the absolute magnitude of the electric field in the brain.Compared to the large electrodes of FIG. 9, high electric fields areconfined to a small volume underneath the electrodes 605.

In an alternative embodiment, similar targeting is achieved with tworing electrodes in a concentric arrangement that is also an effectiveembodiment for a single enclosure TES assembly. FIGS. 11A-D shows theresults of FEM analysis with a Standard Model 701 concentric ringelectrodes. The anode 703 (radius 1 cm) is placed over the premotorcortex. The cathode 702 (inner radius 1.5 cm, outer radius 4 cm)surrounds the cathode. FIG. 11B shows the electric potential on thescalp by shading. The potential of the anode is set to 1 Volt 704 andthe potential of the cathode is set to 0 Volt. FIG. 11C shows thedistribution of electric potential in the brain. High potentials 705occur underneath the anode. FIG. 11D shows the absolute magnitude of theelectric field in the brain. Shown is the absolute magnitude of theelectric field. High electric field strengths are confined to a limitedarea underneath the concentric electrode configuration.

Changing the relative size of the concentric electrodes is effective foraltering the size of the area stimulated. FIGS. 12A-D use a StandardModel 801 with a large central anode 803 (radius 3 cm) placed overpremotor cortex and a thin outer electrode 802 (inner radius 3.5 cm,outer radius 4 cm). A broad cortical area is activated. FIG. 12B showselectric potential on the scalp. The potential of the anode is set to 1Volt 804 and the potential of the cathode is set to 0 Volt. FIG. 12Cshows electric potential in the brain. The area of high potential 805 islarger spatially compared to the configuration in FIGS. 11A-D. FIG. 12Dshows the absolute magnitude of electric fields in the brain. The areaof strong electric fields 806 is more extended compared to theconfiguration in FIGS. 11A-D. By changing the relative sizes of theelectrodes the electric field distribution in the brain can be focusedor defocused.

It will be appreciated that each electrode configuration and combinationof electrode configurations described herein can be used with any otherembodiments of stimulation devices or protocols described herein.

An alternative embodiment of a disposable electrical stimulation deviceis shown in FIG. 13. Six electrodes are arranged in a concentric mannerwith five electrodes 904 surrounding a central electrode 906 in a fixedpentagram arrangement. In some embodiments, all surrounding electrodes904 are configured as cathodes and the central electrode 906 is theanode. The electrodes can be foam electrodes. In some embodiments, allsurrounding electrodes 904 are configured as anodes and the centralelectrode 906 is the cathode. In an alternative embodiment, some of thesurrounding electrodes 904 form a set with the central electrode 906 aseither the anode (or cathode) and one or more of the remainingelectrodes is the cathode (or anode). The flex portion comprising theelectrodes 904 may conform to the curvature of a body part (e.g., thehead). The flex circuit 903 incorporates electrical conductive wiresused to transmit stimulation from an electrical circuit 905. In someembodiments the electrical circuit is constructed on a printed circuitboard (PCB) or silicon chip. The electrical circuit includes a battery902. In some embodiments, there is an on/off switch 901 for the user tocontrol activation of the electrical stimulation system. In theschematic of FIG. 13, a housing for the assembly is not shown.

In an alternative embodiment, the system is semi-disposable. FIG. 14Ashows the same six electrode 1004 configuration as FIG. 13 and alsoincorporates a battery 1006 in the flex circuit 1003 portion of theassembly. The battery 1006 and the electrodes 1004 are disposable. Theflex portion comprising the electrodes 1004 may conform to the curvatureof a body part (e.g., the head). The electrodes 1004 can connect to theflex circuit 1003 using a connector (e.g., a micro snap). A connector1002 is used to interface with a rigid board containing electricalcomponents for achieving the desired form of electrical stimulation 1005and an on/off switch 1001 for user actuated control of the system. Thedisposable flex circuit can be disconnected from the reusable printedcircuit board (or other electrical circuit assembly) 1005 at theconnector 1002. As shown in FIG. 14B, in some embodiments, the flexcircuit 1003 is longer and shaped to go behind a subject's ear in asimilar fashion to an eyeglass frame. The flex circuit can be any shapefor convenience and comfort of placing the assembly on the user's head.

An embodiment of a fully disposable stimulation device designed to becontained in a single housing with a small cross-sectional area(footprint) is shown in FIGS. 15A-D. FIG. 15A depicts a top view of thedevice, showing the on/off switch 1106 on the circuit board 1101. FIG.15A also illustrates the connector 1107 connecting the circuit board1101 to the flex circuit 1103. FIG. 15B depicts a bottom view showingthe electrodes 1102 and flex circuit 1103 beneath the circuit board1101. FIGS. 15C and D depict views of the profile of the device.

FIGS. 16A-23 illustrate an alternative embodiment of a semi-disposablestimulation device. In this embodiment, an optional blister pack 1202,shown in FIGS. 16A and B, is configured to protect a disposable portion1204 of a puck and keep the disposable portion clean (or even sterile)prior to contact with the skin of a user. FIG. 16B illustrates thedisposable portion 1204 positioned within the blister pack 1202.Further, the disposable portion 1204 of the stimulation device comprisesa flexible support disk (FIG. 17), having one or more relief cuts toincrease flexibility of the device, allowing for more conformalattachment to a user's head or other body part. Electrical contact bands1206 may be present in the disposable portion, allowing for electricalcontact with the main housing of the device of the present embodiment.

As shown in FIG. 18A, the disposable portion 1204 in the presentembodiment is configured to snap into the main housing 1208 of thedevice. FIG. 18B shows the disposable portion 1104 snapped into positionwithin the main housing of the stimulation device. Once inserted intothe main housing, an optional backer 1210, shown in FIG. 19A may beremoved from the side of the disposable portion that is opposite to themain housing side, revealing one or more electrodes 1212 and an adherent1214 (e.g., adhesive foam), shown in FIG. 19B. The adherent andelectrodes are configured to be removably or reversibly secured to theskin of a user through the application of a mild to moderate amount offorce. As indicated by the arrows in FIG. 20A, the force can be appliedto a first spot and then in a circular pattern around the housing 1208.As shown in FIG. 20B, the adherent 1214, electrodes 1212, and/or backer1210 may gap depending on the curvature of the body part onto which itis placed.

Continuing from the example and embodiment above, FIG. 21 shows thedisengagement of the disposable portion from the main housing. A usercan push the center of the disposable portion, indicated with an arrowin FIG. 21, to release the housing 1208 from the disposable portion1204. FIG. 22 shows the disengagement of the disposable portion 1204from the skin of the user by peeling the portion 1204 from the skin.

According to an embodiment of the present invention, FIGS. 23A and 23Bshow the location of an integrated replaceable or disposable battery1216 on the underside of the device housing 1204. FIG. 23A illustratesthe battery door 1218 open, while FIG. 23B illustrates the battery door1218 closed.

In some embodiments, the device electrode assembly incorporates tracksfor moving one or more electrodes. FIG. 24 shows an embodiment of a fourelectrode configuration but a similarly configurable system can use anynumber of electrodes. Electrodes on the outer track 1301 can move aroundthe assembly 1303 along a track 1302. In various embodiments, the threeouter electrodes are equidistant from each other (FIGS. 24A, 24D) orgrouped asymmetrically (FIGS. 24B, 24C, 24E, 24F). In some embodiments acentral electrode 1305 can also move laterally along a track 1307 untilstopped by a tab or other mechanical component 1304. By moving theposition of both the central electrode and the surrounding electrodes, arich set of stimulation areas and directions can be achieved in theunderlying brain tissue.

FIGS. 25A-25C illustrate embodiments of configurable electrodeconfigurations for use with the stimulation devices described herein.The electric field induced in neural tissue by transdermal electricalstimulation can depend on the relative surface area and positioning ofthe anode and cathode. Modeling and experimental results indicate thatthe magnitude of the electric field around a given electrode (anode orcathode) is directly related to the current density (currentstrength/electrode area) at that electrode. Moreover, the spatial spreadof direct current stimulation over the cortical surface around a givenelectrode is directly related to the area of the electrode. Thus, forexample, given constant current, a small anode (e.g. FIG. 25A electrodeA in each of the subpanels) and large cathode (e.g. FIG. 25A electrodesB+C+D in each of the subpanels) will maximize both the stimulationintensity and spatial resolution of the anodic effect, whereas a largeanode (e.g. combined electrodes A+B+C in FIG. 25A) and small cathode(e.g. electrode D in FIG. 25A) will maximize the stimulation intensityand spatial resolution of the cathodic effect. Furthermore, by keepingthe current and size of the cathode constant (e.g. electrode D in FIG.25A) and manipulating the size of the anode (e.g. electrodes C+B+A vs.electrodes B+A vs. electrode B in FIG. 25A), it is possible toeffectively zoom in on a region for anodic stimulation (in this casenear electrode B). These examples illustrate the possibilities thatresult from being able to flexibly adjust the role of each electrode (aspart of the anode, part of the cathode, or inactive) with the touch of abutton or under the control of an algorithm. Since the parameters ofeffective stimulation are likely to vary between people and within thesame person for different tasks, effective stimulation may requireadjusting the site(s), extent, and current density in a givenindividual.

In some embodiments, the focality of stimulation can be controlled for afixed set of electrodes by changing which electrodes serve as anodes orcathodes. In an embodiment, the electrodes are concentric 1401 1402 14031404 and connect 1405 to gates or switches 1406 that determine whether aparticular electrode is connected to the positive 1408 or negative 1407terminal. This allows adjusting focus or direction of the electric fieldwithout requiring changing the placement of the electrodes or changingthe peak current. This adjustment could be done by the user, by pressinga button or automatically by the system. The general idea is to havemultiple gates in the PCB that allow connecting or disconnecting thepositive and negative leads to any set of the electrodes, thusspecifying each electrode as part of the anode, part of the cathode, orinactive. A similar configurable system for focusing electric fields canbe achieved with a triangle configuration, as shown in FIG. 25B or pieconfiguration, as shown in FIG. 25C of electrodes.

In some embodiments, application software (e.g., an ‘app’) installed ona PC, laptop, smartphone, tablet, or other computerized platform runningan iOS, Android, Windows or other operating system is configured totransmit a time-varying voltage or current signal through the headphonejack output or other plug interface on the device. This applicationsoftware may be configured as non-transitory control logic that causesthe processor (e.g., of the computer, smartphone, etc.) to perform thefunctional and transformative steps described herein. For example insuch embodiments, the timing and amplitude of stimulation by the devicecan be transmitted from the remote processor executing the controllogic. In an embodiment, the trigger signal is transmitted wirelessly bythe smartphone or tablet via Bluetooth low energy (BTLE) or anotherwireless communication protocol. In an embodiment, the stimulationdevice is powered by a USB or other wired communication port of the PC,laptop, smartphone, tablet, or other computerized platform. In anembodiment, specialized hardware permits analog communication via theheadphone jack such as the HiJack system developed at the University ofMichigan and available via Seeed Studios. In this manner, controlsignals for the timing, intensity, pulsing, or alternating currentcarrier frequency can be generated by the mobile device and transmitteddirectly to the electrical circuitry of the stimulation device.Configurations that use a smartphone, tablet, laptop, or other externalprocessor can be advantageous, because they remove the requirement for amicrocontroller in the electrical circuit of the stimulation device byshifting the processing burden to the mobile device. In someembodiments, a program running on a desktop or laptop computer transmitsa control signal for the stimulation device via serial, USB, or othertransmission protocol.

FIGS. 27A-27D schematically illustrate the operation of an apparatus asdescribed herein to evoke a desired cognitive response. FIGS. 27C and27D in particular illustrate variations in which a remote processor totransmit control information to a lightweight, wearable apparatus toproduce a cognitive effect as described herein.

FIG. 27A shows an exemplary workflow for configuring, actuating, andending a TES session using an apparatus as described herein. Forexample, in FIG. 27A, a subject (e.g., “user”) may input controlinformation directly on an apparatus being worn by the user, or mayinput control information wirelessly by connecting to a remote controlunit 200.

In any of the apparatuses described herein, the apparatus may include aninput to the controller/processor, which may be referred to as a controlinput; the control input may be a manual input on the device (e.g.,button, dial, switch, etc.) or it may be a wireless receiver, receivingwireless information (or both).

In some variations, the remote processor can be used to select a desiredcognitive effect 201 which corresponds to the electrode configurationsetup 202 to achieve the desired cognitive effect. In operation, thismay include selection of electrodes or a TES system that containselectrodes and determination of correct positions for electrodes. InFIGS. 27A-27D the TES system referenced may include any of theapparatuses described herein. The user may be provided configurationinstructions 203 by one or more ways, as indicated in FIG. 27A,including but not limited to: instructions provided via user interface;kit provided to user; wearable system configured to contact TESelectrodes to appropriate portions of a user's body; electrode choiceand positioning done autonomously by user (e.g. due to previousexperience with TES); assistance provided by skilled practitioner ofTES; and instructions provided via other means.

Based on these instructions or knowledge, a subject (or technician) mayposition electrodes on body 204. The apparatuses and method of usingthem described herein may advantageously be self-applied by the subject,although a third party may also apply the device (or assist inapplication). In some embodiments, the TES session starts 207automatically after electrodes are positioned on the body. In otherembodiments, the impedance of the electrodes 205 is checked by a TESsystem before the TES session starts 207. In some embodiments, afterimpedance of the electrodes 205 is checked by a TES system, useractuates TES device 206 before the TES session starts 207. In otherembodiments, after positioning electrodes on the body 204 the useractuates the TES device 206 to start the TES session 207. Once the TESsession starts, the next step is to deliver electrical stimulation withspecified stimulation protocol 208. In some embodiments, a user actuatesend of TES session 209. In other embodiments, the TES session endsautomatically when the stimulation protocol completes 299.

FIG. 27B shows another variation of a wearable, lightweight apparatus(“TES system”) 300. In this variation, adherent electrodes 301 connectto controller 304 via connectors 302 and/or one or more cables (e.g.,wires 303). The primary unit includes a controller 304 and may includeseveral additional components including battery or protected AC powersupply 305, fuse and other safety circuitry 307, memory 308,microprocessor 309, user interface 310, current control circuitry 306,and waveform generator 311.

FIG. 27C shows a TES system comprising an adherent or wearable TESdelivery unit 400 that communicates wirelessly withmicroprocessor-controlled control unit 409 (e.g. a smartphone running anAndroid or iOS operating system such as an iPhone or Samsung Galaxy, atablet such as an iPad, a personal computer including, but not limitedto, laptops and desktop computers, or any other suitable computingdevice). In this exemplary embodiment, adherent or wearable TES deliveryunit 400 holds two or more electrodes in dermal contact with a subjectwith one or more of: an adhesive, a shaped form factor that fits on oris worn on a portion of a user's body (e.g. a headband or around-the-ear‘eyeglass’ style form factor). The TES delivery unit 400 may include:battery 401, memory 402, microprocessor 403, user interface 404, currentcontrol circuitry 405, fuse and other safety circuitry 406, wirelessantenna and chipset 407, and waveform generator 416. The remotemicroprocessor-controlled control unit 409 may include: wireless antennaand chipset 410, graphical user interface 411, one or more displayelements to provide feedback about a TES session 412, one or more usercontrol elements 413, memory 414, and microprocessor 415. As describedherein, the TES delivery unit 400 may include additional or fewercomponents.

A wearable TES delivery unit 400 may be configured to communicatebidirectionally (e.g. duplex) with wireless communication protocol 408to microprocessor-controlled system 409. The system can be configured tocommunicate various forms of data wirelessly, including, but not limitedto, trigger signals, control signals, safety alert signals, stimulationtiming, stimulation duration, stimulation intensity, other aspects ofstimulation protocol, electrode quality, electrode impedance, andbattery levels. Communication may be made with devices and controllersusing methods known in the art, including but not limited to, RF, WIFI,WiMax, Bluetooth, BLE, UHF, NHF, GSM, CDMA, LAN, WAN, or anotherwireless protocol. Pulsed infrared light as transmitted for instance bya remote control is an additional wireless form of communication. NearField Communication (NFC) is another useful technique for communicatingwith a neuromodulation system. One of ordinary skill in the art wouldappreciate that there are numerous wireless communication protocols thatcould be utilized with embodiments of the present invention, andembodiments of the present invention are contemplated for use with anywireless communication protocol.

In some variations, the apparatuses (e.g., TES delivery unit 409) do notinclude a user interface 404 and is controlled exclusively throughwireless communication protocol 408 to control unit 409. In somevariations, the apparatus (e.g., a wearable TES delivery unit 409) doesnot include wireless antenna and chipset 407 and is controlledexclusively through user interface 404.

The pattern of currents delivered into tissue of a subject (e.g.transcranially into the brain) may depend on the electrode configurationand stimulation protocol. For example, an electrode configuration may beused with one or more set of parameters. The set of parameters may beselected based on the desired cognitive effect and the number ofelectrodes, positions of electrodes, sizes of electrode, shapes ofelectrode, composition of electrodes, and anode-cathode pairing ofelectrodes (i.e. whether a set of electrodes is electrically coupled asan anode or cathode; also whether multiple independent channels ofstimulation are present via current sources driving independentanode-cathode sets). A stimulation protocol may define the temporalpattern of current delivered to an anode-cathode set and can incorporateone or more waveform components selected from the list including but notlimited to: direct current, alternating current, pulsed current, linearcurrent ramp, nonlinear current ramp, exponential current ramp,modulation of current, and more complex (including repeated, random,pseudo-random, and chaotic patterns). In operation, the device mayprovide current flow at target areas (e.g., in the brain) to induceneuromodulation when appropriate electrode configurations andstimulation protocols are delivered.

FIG. 27D schematically illustrates a method of operating a remoteprocessor to provide control information to a wearable, lightweightapparatus as described herein. For example, the apparatus (“TES device”)may be paired with the remote device 2701. The user (subject) may thenselect the desired cognitive effect (“form of neuromodulation”) and/orthe control parameters 2703. In some variations the control parametersfor a particular cognitive effect may be predetermined; however, theuser may modify them from this predetermined baseline in somevariations. The subject may then initiate the session or indicate thestart time (e.g., after a delay) 2705.

Any of these control steps 2703, 2705 may be performed via a userinterface. Further, the user interface may include features availablebefore/during the session 2707, and/or after the session 2721. Forexample, feedback during the session may include intensity control 2709,a timer 2711, user feedback collection/monitoring 2713, and stop/cancelcontrol 2715. User interface features available after the session mayinclude feedback about the electrical stimulation 2723, historicalinformation about the operation of the apparatus 2725, and user controlsto repeat prior session parameters 2727. The remote processor may alsobe controlled to communicate wirelessly with the apparatus 2735 and tocontrol the delivery of electrical stimulation to the subject 2737 aswell as control (and indicate) when the session is complete 2799. Theapparatus may also include a stop override (not shown) to stopstimulation immediately, regardless of the control from the remoteprocessor.

Another variation of a lightweight, wearable and self-containedelectrical stimulation apparatus is shown in FIG. 28A. In this example,the apparatus includes a primary unit 3300 housing a power source,processor/controller, and wireless communication module. The outerhousing of the apparatus includes an indicator 3305 which can beilluminated when the device is on and ready to operate; an LED light mayindicate status (e.g., on/off, transmit/receive, etc.). The primary unitalso includes an electrode that can be placed in contact with thesubject's skin, as illustrated in FIG. 28B. A secondary unit 3301 isconnected to the primary unit by a cable 3302. The secondary unit alsoincludes an electrode and can be adhesively attached to the subject. Inthis example, the primary unit 3300 is connected to the subject'sneck/shoulder region and the secondary unit 3301 is independentlypositioned and adhesively connected to the subject's head, asillustrated in FIG. 28B. The positions of the primary and secondaryunits may be reversed.

In some embodiments configured to be powered by a USB or otherconnection to a computerized system, electrical isolation hardware isincorporated in the stimulation device to protect the user fromunexpected electrical surges and voltage boosting hardware is optionallyconfigured to boost 1V, 3V, 5V, or other low voltage inputs to about 9Vor about 12V or another higher voltage level.

In some embodiments, the device comprises sensors and related componentsto record measurements related to brain activity, detect skinresistance, salinity, or humidity, temperature, electromyogram (EMG),galvanic skin response (GSR), heart rate, blood pressure, respirationrate, pulse oximetry, pupil dilation, eye movement, gaze direction ormeasure other physiological or ambient signals. For example, in someembodiments, the device may be configured to perform anelectroencephalogram (EEG). The stimulation device can include sensorsand electrical control and signal processing hardware.

In some embodiments, the stimulation protocol is adjusted based on aphysiological measurement of the body that takes the form of one or moremeasurements chosen from the group of: electromyogram (EMG), galvanicskin response (GSR), heart rate, blood pressure, respiration rate, pulseoximetry, pupil dilation, eye movement, gaze direction, or otherphysiological measurement known to one skilled in the art. For example,the device may be configured to utilize the one or more physiologicalmeasurements to start or stop one or more functionalities (e.g., beginor end a stimulation session).

In some embodiments, a physiological or cognitive measurement is used todetect a cognitive state of the user. For example, in an embodiment, theunit turns on when the user is tired and is configured to increase auser's energy, alertness, and/or wakefulness. In another embodiment,anxiety or stress is detected in a user by measuring galvanic skinresponse or another physiological measurement that correlates anxiety orstress, and the stimulation device is configured to reduce anxietyand/or stress. In another embodiment, the device is configured to modifythe amplitude or phase of a brain rhythm. For instance, in anembodiment, the device can be triggered to enhance synchrony in analpha, beta, or gamma frequency band to affect attention, workingmemory, and/or decision-making.

In some embodiments, the placement of electrodes is adjusted based on aprocedure that delivers a test pulse of known electrical current throughone or more electrodes and measures the induced electric field.

In some embodiments, a stimulation device is configured for therapeuticuse in a user who is a patient. In some embodiments of the invention,the device is configured for use by a consumer without oversight by atechnician, medical professional, or other skilled practitioner.

In some embodiments, targeted stimulation is combined with otherneuromodulatory stimulation techniques to achieve effects in the brain.These embodiments are advantageous for neuromodulation that is notpossible with either effect by itself. Other brain stimulationmodalities include transcranial ultrasound neuromodulation, transcranialmagnetic stimulation (TMS), deep brain stimulation (DBS), optogeneticstimulation, one electrode or an array of electrodes implanted on thesurface of the brain or dura (electrocorticography (ECoG) arrays), andother modalities of brain stimulation known to one skilled in the art.

In some embodiments, the one or more effects of using multiple fauns ofneuromodulation are chosen from the list of: increasing the spatialextent of stimulation; decreasing the spatial extent of stimulation;reshaping the spatial extent of stimulation; modifying the nature of theinduced neuromodulation; increasing the intensity of neuromodulation;decreasing the intensity of neuromodulation; mitigating a cognitive orbehavioral affect; enhancing a cognitive or behavioral affect; modifyingthe cells affected by neuromodulation; modifying the cellularcompartments affected by neuromodulation; or another modification of theneuromodulating energy transmitted into the brain and/or nervous system.

Combining targeted stimulation with transcranial ultrasoundneuromodulation can be advantageous for more effectively targeting thetemporal and/or spatial extent of neuromodulation. Combining targetedstimulation with transcranial ultrasound neuromodulation can also bebeneficial for shaping the induced cognitive, behavioral, perceptual,motor, or other change in brain function. For instance, stimulationcould be used to “clamp” shallow areas near the brain surface so that nochange in brain function occurs during the transmission of ultrasound toa deeper brain region desired to be affected by transcranial ultrasoundneuromodulation. In another embodiment of the invention that combineselectrical stimulation and transcranial ultrasound neuromodulation,supralinear enhancement of neuromodulation is achieved so that lowenergy levels to improve the safe operation of the system. In anembodiment, components for delivering transcranial ultrasoundneuromodulation are integrated in an electrical stimulation device.

In some embodiments, neuromodulation is targeted to more than one brainregion or other portion of the nervous system (e.g. spinal cord orcranial nerves). In some embodiments, targeted stimulation or anothertechnique for neuromodulation targets a first brain region to induce aset of behavioral, cognitive, or other effects, while concurrently (orin close temporal relation) targeting a second brain region tocounteract a subset of the effects of stimulation targeting the firstbrain region. In this manner, the functional effect of neuromodulationcan be shaped to reduce unwanted side effects. In some embodiments thattarget multiple brain regions, the brain regions are anatomically nearbybrain regions. In other embodiments that target multiple brain regions,the brain regions are anatomically distant brain regions.

In some embodiments of the invention in which multiple brain regions aretargeted with a pre-defined temporal relationship, the device isconfigured to target a first brain region and a second brain region tocounteract an unwanted effect occurring in or mediated by the secondbrain region caused by stimulation of the first region. In someembodiments of the invention in which multiple brain regions aretargeted with a pre-defined temporal relationship, the device isconfigured to target additional brain regions to counteract the effectsof stimulating a first and/or second brain region. In some embodimentsof the invention in which multiple brain regions are targeted with apre-defined temporal relationship, the device is configured forconcurrent stimulation of the first and second brain regions. In someembodiments of the invention in which multiple brain regions aretargeted with a pre-defined temporal relationship, the device isconfigured such that stimulation of the first and second brain regionsoccurs with a specified latency, where the latency is chosen from thegroup of: less than about 30 seconds; less than about 10 seconds; lessthan about 5 seconds; less than about 1 second; less than about 500milliseconds; less than about 250 milliseconds; less than about 100milliseconds; less than about 50 milliseconds; less than about 40milliseconds; less than about 30 milliseconds; less than about 20milliseconds; less than about 10 milliseconds; less than about 5milliseconds; less than about 2 milliseconds; or less than about 1millisecond.

In some embodiments of the invention in which multiple brain regions aretargeted with a pre-defined temporal relationship, parameters ofstimulation of multiple brain regions and relative timing of stimulationare determined based on feedback from a measurement of brain activity,behavior, cognition, sensory perception, motor performance, emotion, orstate of arousal.

In some embodiments, the device is configured to induce spike-timingdependent plasticity in one or more targeted brain regions. In someembodiments for inducing spike-timing dependent plasticity, the deviceis configured to re-create patterns of neural activity in and/or betweendistinct brain regions during which transduction delays of between about1 ms and about 30 ms occur.

In some embodiments, random noise stimulation is delivered. Random noisestimulation has been shown to induce neuroplasticity (Terney et al.,2008). Advantageous embodiments that use random noise stimulationdelivered by TES target specific brain regions for neuroplasticity orbroader areas as large as a cortical hemisphere or the entire brain.

In some embodiments, the timing of targeted stimulation is designed tomodulate brain activity that occurs in the temporal domain. In someembodiments, stimulation is used to activate, inhibit, or modulate brainrhythms in one or more brain regions. In some embodiments, stimulationis targeted to multiple connected regions in the brain that normallycommunicate with a known temporal latency. By stimulating multiple brainregions, communication or coupling between disparate brain regions canbe enhanced, disrupted, phase-shifted or otherwise modulated.

In some embodiments, brain recordings are used to measure the effect oftargeted stimulation. This technique is advantageous for providingfeedback (in some embodiments, real-time feedback) concerning thetargeting, timing, and stimulation parameters for targeted stimulationand/or other techniques for neuromodulation used. In this embodiment ofthe invention, the measurement of brain activity takes the form of oneor a plurality of: electroencephalography (EEG), magnetoencephalography(MEG), functional magnetic resonance imaging (fMRI), functionalnear-infrared spectroscopy (fNIRS), positron emission tomography (PET),single-photon emission computed tomography (SPECT), computed tomography(CT), functional tissue pulsatility imaging (fTPI), xenon 133 imaging,or other techniques for measuring brain activity known to one skilled inthe art.

In some embodiments, the effect on the brain is measured by a cognitiveassessment that takes the form of one or more of: a test of motorcontrol, a test of cognitive state, a test of cognitive ability, asensory processing task, an event related potential assessment, areaction time task, a motor coordination task, a language assessment, atest of attention, a test of emotional state, a behavioral assessment,an assessment of emotional state, an assessment of obsessive compulsivebehavior, a test of social behavior, an assessment of risk-takingbehavior, an assessment of addictive behavior, a standardized cognitivetask, an assessment of “cognitive flexibility” such as the Stroop task,a working memory task (such as the n-back task), tests that measurelearning rate, or a customized cognitive task.

In some embodiments, physiological monitoring is used to measure theeffect of electrical stimulation. This technique is advantageous forproviding feedback (in some embodiments, real-time feedback) concerningthe targeting, timing, and stimulation parameters for targetedstimulation and/or other techniques for neuromodulation used. In thisembodiment of the invention, the measurement of physiological signalstakes the form of one or a plurality of: electromyogram (EMG), galvanicskin response (GSR), heart rate, blood pressure, respiration rate, pulseoximetry, pupil dilation, eye movement, gaze direction, or otherphysiological measurement known to one skilled in the art.

In another aspect of an embodiment of the invention, a device assists auser or other individual in placing electrodes at appropriate locationsto achieve a desired form of neuromodulation. Methods for guiding theuser or other individual to place electrodes at the one or more desiredlocations includes one or more from the group of: fiduciary markers onthe head; ratiometric measurements relative to fiduciary markers on thehead; alignment components that detect relative location of electrodecomponents by proximity as measured by radiofrequency energy,ultrasound, or light; or a grid or other alignment system, such as theposition of the electrodes themselves, projected onto the head of theuser. In some embodiments of the invention, an indicator providesfeedback when the electrode positioning is achieved through a light-,sound-, or tactile-based indicator.

In some embodiments of the invention, a user or other individualidentifies fiduciary markers to assist in targeting. Fiduciary markerson the head include those used for placing EEG electrodes in thestandard 10/20 arrangement. The nasion is the point between the foreheadand the nose. The inion is the lowest point of the skull from the backof the head and is normally indicated by a prominent bump.

In some embodiments, neuromodulation is achieved exclusively viaelectrodes placed on portions of the head, face, and neck that do nothave hair to reduce the need for additional material or systemcomponents for coupling the electrical current to the scalp. Targetedstimulation is achieved with a system that includes one or moreelectrodes placed on hairless portions of the head, face, and neck. Insome embodiments, an electrode placed on the periphery (below the neck)is used to deliver a spatially broad electrical field to the brain.

In some embodiments of the invention, multiple stimulation devices areused to deliver a focused electric field to a deeper brain region. Onemethod for targeting an electrical field at depth in the brain is todeliver AC from multiple sets of electrodes and select anode-cathodepairs, stimulus amplitude and frequency, and relative timing or phasedelay of stimulation so that constructive and destructive interferenceamong transmitted electric fields create a focused region ofneuromodulation. In some embodiments, a master device controls thetiming and stimulus parameters among one or more slave devices in orderto achieve improved focusing of stimulation.

In another aspect of an embodiment of the invention, the placement ofelectrodes and spatiotemporal pattern of stimulation delivered throughthe electrodes is configured for targeting the ventromedial prefrontalcortex for neuromodulation (VmPFC; Brodmann area 10). Targeting to theVmPFC can be advantageous for modulating emotion, risk, decision-making,and fear.

In another aspect of an embodiment of the invention, the placement ofelectrodes and spatiotemporal pattern of stimulation delivered throughthe electrodes is configured for targeting the orbitofrontal cortex forneuromodulation (OFC; Brodmann 10, 11, 14; 16). Targeting to the OFC canbe advantageous for modulating executive control and decision making.

In some embodiments, the system or device is configured to target one ormore regions of cerebral cortex, where the region of cerebral cortexchosen from the group of: striate visual cortex, visual associationcortex, primary and secondary auditory cortex, somatosensory cortex,primary motor cortex 4, supplementary motor cortex, premotor cortex, thefrontal eye fields, prefrontal cortex, orbitofrontal cortex,dorsolateral prefrontal cortex, ventrolateral prefrontal cortex,anterior cingulate cortex, and other area of cerebral cortex.

In some embodiments, the system or device is configured to target one ormore deep brain regions chosen from the group of: the limbic system(including the amygdala), hippocampus, parahippocampal formation,entorhinal cortex, subiculum, thalamus, hypothalamus, white mattertracts, brainstem nuclei, cerebellum, neuromodulatory nucleus, or otherdeep brain region.

In some embodiments, the system or device is configured to target one ormore brain regions that mediate sensory experience, motor performance,and the formation of ideas and thoughts, as well as states of emotion,physiological arousal, sexual arousal, attention, creativity,relaxation, empathy, connectedness, and other cognitive states.

In some embodiments, modulation of neuronal activity underlying multiplesensory domains and/or cognitive states occurs concurrently or in closetemporal arrangements.

In some embodiments, a device can be configured via a user interface onthe device (e.g., selector switch) or wireless interface via anotherdevice (e.g. smartphone, tablet, laptop, or desktop computer) fortargeting a particular brain region. For instance, a user may be able toconfigure the particular type of neuromodulation utilized by using asmartphone application connected to an application programming interface(API) provided by the device over a wireless connection via a local areanetwork. In this manner, the device can be conveniently changed betweentwo or more types of stimulation.

In some embodiments, coupling between a stimulating electrode and theskin is achieved with a semi-permeable sack between the electrode andthe skin that releases a small amount of water or other conductiveliquid when squeezed. In some embodiments of this aspect of theinvention, the water or other conductive liquid evaporates after the TESsession and does not require cleanup.

While multiple embodiments are disclosed, still other embodiments of thepresent invention will become apparent to those skilled in the art fromthis detailed description. The invention is capable of myriadmodifications in various obvious aspects, all without departing from thespirit and scope of the present invention. Accordingly, the drawings anddescriptions are to be regarded as illustrative in nature and notrestrictive.

When a feature or element is herein referred to as being “on” anotherfeature or element, it can be directly on the other feature or elementor intervening features and/or elements may also be present. Incontrast, when a feature or element is referred to as being “directlyon” another feature or element, there are no intervening features orelements present. It will also be understood that, when a feature orelement is referred to as being “connected”, “attached” or “coupled” toanother feature or element, it can be directly connected, attached orcoupled to the other feature or element or intervening features orelements may be present. In contrast, when a feature or element isreferred to as being “directly connected”, “directly attached” or“directly coupled” to another feature or element, there are nointervening features or elements present. Although described or shownwith respect to one embodiment, the features and elements so describedor shown can apply to other embodiments. It will also be appreciated bythose of skill in the art that references to a structure or feature thatis disposed “adjacent” another feature may have portions that overlap orunderlie the adjacent feature.

Terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention.For example, as used herein, the singular forms “a”, “an” and “the” areintended to include the plural forms as well, unless the context clearlyindicates otherwise. It will be further understood that the terms“comprises” and/or “comprising,” when used in this specification,specify the presence of stated features, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, steps, operations, elements, components, and/orgroups thereof. As used herein, the term “and/or” includes any and allcombinations of one or more of the associated listed items and may beabbreviated as “/”.

Spatially relative terms, such as “under”, “below”, “lower”, “over”,“upper” and the like, may be used herein for ease of description todescribe one element or feature's relationship to another element(s) orfeature(s) as illustrated in the figures. It will be understood that thespatially relative terms are intended to encompass differentorientations of the device in use or operation in addition to theorientation depicted in the figures. For example, if a device in thefigures is inverted, elements described as “under” or “beneath” otherelements or features would then be oriented “over” the other elements orfeatures. Thus, the exemplary term “under” can encompass both anorientation of over and under. The device may be otherwise oriented(rotated 90 degrees or at other orientations) and the spatially relativedescriptors used herein interpreted accordingly. Similarly, the terms“upwardly”, “downwardly”, “vertical”, “horizontal” and the like are usedherein for the purpose of explanation only unless specifically indicatedotherwise.

Although the terms “first” and “second” (or primary and secondary) maybe used herein to describe various features/elements, thesefeatures/elements should not be limited by these terms, unless thecontext indicates otherwise. These terms may be used to distinguish onefeature/element from another feature/element. Thus, a firstfeature/element discussed below could be teemed a secondfeature/element, and similarly, a second feature/element discussed belowcould be termed a first feature/element without departing from theteachings of the present invention.

As used herein in the specification and claims, including as used in theexamples and unless otherwise expressly specified, all numbers may beread as if prefaced by the word “about” or “approximately,” even if theterm does not expressly appear. The phrase “about” or “approximately”may be used when describing magnitude and/or position to indicate thatthe value and/or position described is within a reasonable expectedrange of values and/or positions. For example, a numeric value may havea value that is +/−0.1% of the stated value (or range of values), +/−1%of the stated value (or range of values), +/−2% of the stated value (orrange of values), +/−5% of the stated value (or range of values), +/−10%of the stated value (or range of values), etc. Any numerical rangerecited herein is intended to include all sub-ranges subsumed therein.

Although various illustrative embodiments are described above, any of anumber of changes may be made to various embodiments without departingfrom the scope of the invention as described by the claims. For example,the order in which various described method steps are performed mayoften be changed in alternative embodiments, and in other alternativeembodiments one or more method steps may be skipped altogether. Optionalfeatures of various device and system embodiments may be included insome embodiments and not in others. Therefore, the foregoing descriptionis provided primarily for exemplary purposes and should not beinterpreted to limit the scope of the invention as it is set forth inthe claims.

The examples and illustrations included herein show, by way ofillustration and not of limitation, specific embodiments in which thesubject matter may be practiced. As mentioned, other embodiments may beutilized and derived there from, such that structural and logicalsubstitutions and changes may be made without departing from the scopeof this disclosure. Such embodiments of the inventive subject matter maybe referred to herein individually or collectively by the term“invention” merely for convenience and without intending to voluntarilylimit the scope of this application to any single invention or inventiveconcept, if more than one is, in fact, disclosed. Thus, althoughspecific embodiments have been illustrated and described herein, anyarrangement calculated to achieve the same purpose may be substitutedfor the specific embodiments shown. This disclosure is intended to coverany and all adaptations or variations of various embodiments.Combinations of the above embodiments, and other embodiments notspecifically described herein, will be apparent to those of skill in theart upon reviewing the above description.

What is claimed is:
 1. A lightweight and wearable transdermal electricalstimulation device for inducing a cognitive effect in a subject, thedevice comprising: a primary unit including: a power source, acontroller, and a first transdermal electrode; and a secondary unitelectrically connected to the primary unit by a cable extending from theprimary unit, the secondary unit including a second transdermalelectrode; wherein either the primary unit or the secondary unit or bothis configured to be worn on the subject's head or neck, and thesecondary unit is configured to be independently positioned at a secondlocation on the subject so that the controller can drive stimulationbetween the first and second electrodes to induce a cognitive effect inthe subject.
 2. The device of claim 1, wherein the controller isconfigured to apply one or more pre-determined stimulation protocolswhen driving stimulation between the first and second electrodes toinduce a cognitive effect.
 3. The device of claim 1, wherein thesecondary unit is configured to be detachably coupled to the primaryunit before applying the primary and secondary units to the subject. 4.The device of claim 1, wherein the primary unit is configured to beadhesively attached to the subject's head or neck.
 5. The device ofclaim 1, wherein the primary unit and secondary unit together weigh lessthan about 5 ounces.
 6. The device of claim 1, wherein the deviceincludes a visual indicator on an outer surface of the primary unit. 7.The device of claim 1, wherein the device includes an input control onan outer surface of the primary unit.
 8. The device of claim 1, whereinthe first and second electrodes are configured to be disposable anddetachably coupled to the device.
 9. The device of claim 1, wherein thecontroller is configured to adjust current across the first and secondelectrodes based on a detected impedance.
 10. The device of claim 1,wherein the primary unit further comprises a wireless communicationsmodule in communication with the controller and configured to providestimulation instructions to the controller.
 11. The device of claim 1,wherein a maximum thickness of the primary unit is less than about 30mm.
 12. The device of claim 1, wherein the controller is configured tocause alternating current, direct current, or a combination ofalternating and direct current between the first and second electrodes.13. The device of claim 1, wherein the device is configured to applypulsed electrical stimulation.
 14. The device of claim 1, wherein thesecond electrode is configured to be positioned on a neck or head of asubject.
 15. The device of claim 1, wherein the first electrode is partof a replaceable cartridge configured to be detachably coupled to theprimary unit.
 16. The device of claim 1, wherein the first electrode andsecondary unit are part of a replaceable cartridge configured to bedetachably coupled to the primary unit.
 17. A lightweight, wearable, andself-contained transdermal electrical stimulation device for inducing acognitive effect in a subject, the device comprising: a primary unithaving a housing at least partially enclosing: a power source, awireless communications module, a current generator connected to thepower source; a controller configured to receive stimulationinstructions from a remotely located processor via the wirelesscommunications module, and a replaceable cartridge including a firsttransdermal electrode; and a secondary unit electrically connected tothe primary unit by a cable extending from the housing, the secondaryunit including a second transdermal electrode; wherein the primary unitis configured to be worn on the subject's head or neck and the secondaryunit is configured to be independently attached to a second location onthe subject so that the controller controls the current generator todrive stimulation between the first and second electrodes based onstimulation instructions received from the remotely located processor toinduce a cognitive effect in the subject.
 18. A method of inducing acognitive effect in a subject, the method comprising: attaching aprimary unit of a lightweight, wearable, and self-contained transdermalelectrical stimulation device to a first location on the subject's heador neck so that a first electrode of the primary unit contacts thesubject's skin; attaching a secondary unit comprising a second electrodeto a second location on the subject, wherein the secondary unit iselectrically connected to the primary unit by a cable; and drivingstimulation between the first and second electrodes to induce acognitive effect in the subject, wherein a controller in the primaryunit drives stimulation.
 19. The method of claim 18, further comprisingseparating the primary unit from the secondary unit before drivingstimulation between the first and second electrodes.
 20. The method ofclaim 18, wherein attaching the primary unit comprises adhesivelyattaching the primary unit to the subject's head or neck at the firstlocation.
 21. The method of claim 18, wherein attaching the secondaryunit comprises adhesively attaching the secondary unit to the subject.22. The method of claim 18, wherein attaching the secondary unitcomprises attaching the secondary unit to the subject's neck or head.23. The method of claim 18, further comprising wirelessly transmittingstimulation parameters from a mobile communications device to thecontroller in the primary unit.
 24. The method of claim 18, whereindriving stimulation between the first and second electrodes to inducethe cognitive effect in the subject comprises supplying a maximumcurrent of at least 2 mA during stimulation.
 25. The method of claim 18,wherein driving stimulation between the first and second electrodes toinduce the cognitive effect in the subject comprises supplying currenthaving a primary frequency component within the range of about 400 Hz-20kHz.
 26. The method of claim 18, wherein driving stimulation between thefirst and second electrodes to induce the cognitive effect in thesubject comprises supplying current having a primary frequency componentwithin the range of about 500 Hz-10 kHz.
 27. The method of claim 18,further comprising attaching a cartridge including the first electrodeto the primary unit before attaching the primary unit to the subject'shead or neck.
 28. A method of inducing a cognitive effect in a subject,the method comprising: coupling a disposable first electrode anddisposable second electrode to a reusable primary unit of a lightweightand wearable transdermal electrical stimulation apparatus, wherein thedisposable first electrode is coupled to the primary unit via anelectrode connector on the primary unit so that the first electrode isattached to the primary unit and in electrical communication with acontroller in the primary unit, and wherein the second electrode iselectrically connected to the controller via a cable; attaching theprimary unit to a first location on the subject's head or neck so thatthe first electrode contacts the subject's skin; independently attachingthe second electrode to a second location on the subject so that thesecond electrode contacts the subject's skin; and activating thecontroller to drive stimulation between the first and second electrodesto induce a cognitive effect in the subject.